Nadim Michel Daher

When it comes to non-invasively imaging the human body’s internal organs and tissues, we use all kinds of waves and radiations at our disposal. We use X-rays in radiographic or computed tomography (CT) imaging, acoustic waves in ultrasound imaging, magnetic fields in magnetic resonance (MR) imaging, and visible light in optical imaging, along with a few other types of modalities. As for the use of microwaves (or radio waves, or “radar”) in diagnostic imaging applications, it has been experimented with for many years, but has remained confined until recently to the research realm. Now, as it enters into commercialization stage, it’s time to take a closer look at the clinical potential of this new imaging modality.

It turns out that those same types of electromagnetic waves that our cellular phones use to transmit voice and data actually check all the marks for being used as a medical imaging modality: They can penetrate tissue in a non-ionizing and presumably harmless manner, get scattered based on the dielectric properties of tissue, and this scatter can be measured back by radio sensors in order to reconstruct an image.

Like every imaging modality, microwave imaging comes with its strengths and limitations. On the upside, microwave imaging is fast, safe, and can provide powerful functional imaging capabilities in real-time and in three dimensions. Its hardware components come in small sizes and at a low cost, since they benefit from the ongoing miniaturization and cost efficiencies of the large consumer electronics markets of wireless devices. On the downside, the modality provides rather low spatial resolution, and could use a broader body of clinical studies to understand it more fully.

That is about to change. Two startup companies, Micrima from the UK and EMTensor from Austria, were on the exhibit floor of the 2018 European Congress of Radiology to talk about new, largescale clinical studies that are nearing completion, and to showcase clinical imaging systems that are respectively ready, and about to be ready for prime time.

Digital mammography is the established mainstay in breast cancer screening and diagnosis, and the advent of 3D digital breast tomosynthesis over the last few years has been taking the modality to the next level. However, X-ray breast imaging has intrinsic limitations, which various other modalities such as breast ultrasound, breast MRI and molecular breast imaging have been seeking to address. Despite the advances in these various modalities, all of which still have important shortcomings, the position of an effective adjunct to digital mammography remains very much underserved. It is in this context that radio-wave breast imaging is evolving through multiple research and development efforts as detailed in the recent paper “Recent Advances in Microwave Imaging for Breast Cancer Detection”.

The most mature of these is Micrima’s MARIA® breast imaging system, in development for more than a decade and CE-marked since 2015. It uses radio-frequency waves to image the breast in 3D, while providing optimal patient comfort. It does not require breast compression, and the patient is lying down on a table in natural position. The resulting images provide a detailed view of the functional activity in breast tissue, which indicates the presence of lesions. Thanks to the deep penetration of radio-waves in breast tissue, unhampered by bones or air, the modality is effective in various types of breast but particularly effective in dense breasts, which has been a key area of breast imaging needing improvement. Continuing development work involving machine learning is expected to further improve the functional characterization of lesions provided by the system in the very near future. As the company’s new set of ongoing clinical trials in the UK near completion, this new modality is starting to deliver on its high promise for augmenting the breast imaging armamentarium.

Stroke imaging was a hot topic at ECR 2018. Since interventional treatment techniques of stroke have taken off (complementing the more mature intravenous therapy techniques), brain imaging of stroke patients has become a cornerstone of stroke patient management. Indeed, the key to managing stroke patients most effectively is the ability to differentiate between an ischemic or haemorrhagic stroke as quickly as possible, ideally during the critical first hour of crisis, and definitely under the three- to four-hour mark. This is how emergency clinicians can decide whether or not to administer tissue plasminogen activator (tPA) treatment, or whether to send the patient directly to a center equipped to perform endovascular thrombectomy interventions, neurosurgery and neuro-critical care.

Therefore, there is a very strong clinical rationale for an effective imaging modality that can triage stroke patients quickly, as soon as they reach emergency departments or even sooner, such as on board ambulances in mobile stroke units (MSU). EMTensor’s brain imaging system, now in its third-generation with the fourth already in the works, is extremely promising in this regard. The system has a much smaller footprint and considerably lower cost compared to the mobile CT units that are starting to equip ambulances. This makes it much more realistic to envision it as a standard equipment of ambulance fleets. Further, its safety profile makes it suitable for clinical use cases not possible with conventional MRI or CT brain imaging, such as 24/7 brain monitoring of patients with traumatic brain injury. EMTensor seems to be moving in these directions quickly, with two brain scanners used in ongoing clinical studies, and plans for CE-marking and FDA approval within three years.

It’s exciting to be able to witness the debut of a brand new imaging modality and watch it take its first steps into the clinical field. It makes one realize that there are always new avenues for bridging some of the gaps left open by the current spectrum of imaging modalities. The big imaging vendors should take notice of this new versatile, safe and cost-effective modality, which stands a good chance of establishing itself at the frontlines or as an adjunct across various care pathways-potentially disrupting places where ‘big-iron’ modalities are established today.

Articles

ECR 2018: Electromagnetic microwaves bring much-needed new weaponry to the arsenal of breast and stroke imaging.

Microwave Imaging Shows Great Potential

At the HIMSS17 show last March we announced 

the race for medical imaging analytics ecosystems

, and profiled seven vendors making early moves. Eight months later at RSNA 2017, this race continued to pick up steam in a big way.

With a momentum that seems to mirror the rapid proliferation of medical imaging artificial intelligence companies, more and more of the larger informatics vendors are looking to capitalize on these diverse applications to augment their own offerings. As more AI algorithms obtain regulatory approval, the big opportunity now is to channel them to market while delivering them as an integral part of the daily clinical workflows. Indeed, experience has shown that even the smartest computer-aided detection or diagnosis (CADx) algorithm, if not well integrated into the routine workflow, is likely to be ultimately ignored by most clinical end-users.

Therefore, while these algorithms may become validated for market use, they still need a pathway to market adoption and “a place to live” once in the field. It is not reasonable to think that their creators, often startups, have the wherewithal and the market access to channel them into the field. In fact, if they had to switch gears towards the marketing and sales function, they would quickly lose their technological edge and inevitably slow down their product portfolio development. Not counting the fact that, at a time when integrated delivery networks (IDN’s) and health systems are trying to consolidate their vendor relationships and standardize their procurement mechanisms, no one is going to enter into dozens of new vendor contracts to deploy various niche AI applications.[[{"type":"media","view_mode":"media_crop","fid":"64768","attributes":{"alt":"Nadim Michel Daher, Industry Principal Medical Imaging and Informatics, Frost & Sullivan","class":"media-image media-image-right","id":"media_crop_198633661643","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"8297","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 213px; width: 170px; float: right;","title":"Nadim Michel Daher, Industry Principal Medical Imaging and Informatics, Frost & Sullivan","typeof":"foaf:Image"}}]]

Deep learning frameworks provide an efficient way to develop software algorithms, at much higher speed than traditional coding methods. Therefore, the proliferation of medical imaging AI solutions that we saw at RSNA 2017, with a massive number of new players and new algorithms from existing players, is bound to continue. Whether these frameworks are utilized in a supervised or unsupervised (or hybrid) way, what it really boils down to is assembling a robust dataset of images, associated findings, annotations, and outcomes, then let the framework work its magic to identify the relationships between them, and derive the right software code.

That’s where few vendors have identified the opportunity to help AI developers gain cost- and time-efficient access to large, well-curated medical imaging datasets. DICOM Systems with their 

, and Medexprim with their now open-sourced 

, are two such vendors that promoted this value proposition at RSNA. This commercial data access is meant to complement the two strategies for accessing good quality image datasets that early-moving imaging AI vendors have had to rely on: the imaging resources and biobanks available for R&D projects such as 

 on one hand, and on the other hand, one-to-one R&D collaborations between individual hospital organizations and individual vendors.

Just as interesting to see in this context of capitalizing on data, is the growing vendor interest for delivering ways for academic researchers themselves to collaborate, promote and validate their own home-grown advanced algorithms. 

, with a focus on neuroimaging, was created to do just that.

 are all making some good progress, either by adding native applications to their advanced imaging analytics ecosystem, or by expanding their portfolio through new partnerships with  independent software vendors (ISV’s). Notably, Google Health made it as a first-time exhibitor at this year’s RSNA, while NTT Data augmented its AI partner portfolio by integrating

. In parallel, few imaging AI vendors that started out with a single niche application are gradually expanding organically by adding new native modules. A good case in point is Arterys who announced at RSNA it had received FDA approval for its 

, where it will soon roll out its new clearance-pending oncology lung CT and liver CT and MR applications, complementing the FDA-cleared cardiac MR application.

Meanwhile, much of the attention on the RSNA showfloor was drawn towards few new contenders setting out to build their own AI marketplace or “app store”, the top two of which would be:

: Nuance is probably the highest-profile new entrant in this playing field, due to the vast market footprint of the radiology reporting giant. 

Nuance launched its imaging AI Marketplace at RSNA

, dubbed the first “open” marketplace which brings on-board a number of imaging AI algorithms. Concurrently, Nuance also announced two new significant related partnerships, with Philips Healthcare, and with the GPU market leader NVIDIA, both of which strengthen its market entry. Things have shaped up very nicely for Nuance in the imaging analytics area since its 2014 acquisition of image sharing vendor Accelarad (re-branded PowerShare Network).

In fact, Nuance was able to capitalize on two other related acquisitions that were much less promoted publicly, both radiology analytics vendors: that of Montage Healthcare Solutions (re-branded as PowerScribe 360 MONTAGE and mPower), and that of 

. Now, the combination of these image management and analytics capabilities, along with the new partnerships, put Nuance in an ideal position to power-up, populate and operationalize its new imaging AI marketplace.

: EnvoyAI is the new name for McCoy Medical Technologies, which advanced visualization vendor 

 last June but decided to maintain as an independent entity. EnvoyAI’s new Exchange platform is an 

, with over 15 partner ‘apps’ and 35 algorithms, and counting, already accessible through the platform. EnvoyAI also acts as a channel for some native TeraRecon ‘apps’ it contributes to the platform, since two are already part of EnvoyAI’s offering. Synergies could also work the other way for the two companies, since on its side TeraRecon also pre-launched its new Northstar viewer, dubbed the ‘world’s first AI-results viewer’, which will allow for closer interaction between image viewing and these advanced imaging analysis tools.

The company is dedicated to making the use of medical imaging AI algorithms practical for end-users, which means they will be able to experiment with the various algorithms and pay per-use. These prices, determined by each AI vendor, already vary widely across the portfolio. For example, few algorithms are priced under $1 per study, while others, which can be billed for against a CPT reimbursement code, at over $40 per study.

As of the RSNA 2017 timeframe, only a handful of imaging AI algorithms seeking regulated use cases, already have U.S. FDA market approval. While the process is time- and cost-intensive, most vendors seem to have the ball rolling on the process, yet everyone is eagerly waiting for FDA regulation on how to deal with the continuous learning of algorithms, rather than having to re-submit regular “Maintenance 510k” applications for new algorithm versions, as is being done by some right now.

The marketplaces offering access to both FDA-approved and non-FDA approved algorithms raises the question of whether we are bound to enter an interim phase of off-label, experimental use of the regulated yet non-approved ones, as has been largely the case, for example, with image study interpretations in non-diagnostic grade mobile viewers.

RSNA 2017: The Race for Medical Imaging Analytics Ecosystems Takes New Turns

About ten years ago, in what could have been an ordinary 

post, a doctor from Connecticut, Richard L. Reece, wrote these lines:



“If […] you regard patients and doctors as intelligent consumers of care and providers of integrity, who give that care, you may believe they are perfectly capable of fending for themselves.”

Fending for our own selves. This seems to be the impression that the ongoing regulatory debates in the U.S. about concerns surrounding gadolinium retention, is leaving patients with for now. The U.S. FDA has deemed the current clinical evidence as inconclusive of an adverse effect of gadolinium retention in the brain and body, thereby recommending that further research studies be conducted by pharmaceutical vendors, academia, FDA, and federal research centers.  This provisional stance is leaving patients hanging in their decision-making, while everyone waits for more conclusive studies. [[{"type":"media","view_mode":"media_crop","fid":"64768","attributes":{"alt":"Nadim Michel Daher, Medical Imaging Industry Principal at Frost & Sullivan","class":"media-image media-image-right","id":"media_crop_127147805794","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"8297","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 188px; width: 150px; float: right;","title":"Nadim Michel Daher, Medical Imaging Industry Principal at Frost & Sullivan","typeof":"foaf:Image"}}]]

RSNA 2017 did ease some concerns.  The results of a 

by Robert J. McDonald, et al, were released, which finds that gadolinium deposits in the brain are not associated with adverse neurologic outcomes. That’s great news indeed, but it’s only one type of potential adverse outcome. In fact, the same researcher team, in a preclinical study of rodents, is now investigating the infiltration of gadolinium from blood into the cerebrospinal fluid (CSF) as the potential initial pathway entry into the brain.

It’s an uneasy situation for patients right now. We are exposed to an ever-growing body of clinical 

that confirm retention is indeed occurring after multiple injections of gadolinium-based contrast agents (GBCA), even in patients with normal kidney function. We already know that secondary effects could exist (that would be called Gadolinium Deposition Disease [GDD]), and that they have not been documented well enough. And yet, we are being told to wait – hoping the next time we need a contrast-enhanced MRI won’t be too soon.

The actor Chuck Norris deciding to sue GBCA manufacturers and distributors because he and his actor wife are convinced the acute strange symptoms she suffered are secondary effects tied to the three injections of linear GBCAs that she received in a very short time period, now comes in as the cherry on top of this raging issue. As this ad hoc lawsuit starts turning into a wider class action, it is becoming widely publicized that there could also be an acute immune reaction to gadolinium injections in addition to the issue of gadolinium retention, all occurring in patients with normal renal function.

The Evolving GBCA Safety Profile: a Ten-Year Recap


A few months before Dr. Reece’s 2006 post,  the FDA issued a major Black Box warning guiding physicians and patients with renal insufficiency that remains in effect today: these patients risk contracting a potentially fatal disease called nephrogenic systemic fibrosis (NSF). Almost immediately, this led the medical community to cease gadolinium injections in this patient group. The almost overwhelming cases of NSF were associated with the linear (aka open-chain) GBCA agents which bind the gadolinium agent the least tightly, making the binding less stable.

Now, 10 years later, the issue has surfaced for patients with normal renal function that GBCAs, at least the less stable (linear or open-chain) ones, actually leave residual deposits in the brain. So far, most of the clinical studies have demonstrated a potential safety risk profile of gadolinium deposition in the brain with the linear GBCAs, while alluding to a seemingly safer profile of macrocyclic or closed-chained GBCAs having no or less deposition. But just recently, the results of a new 

from Norway were publicized, that may shake-up the soft consensus that seemed to have been reached. That study shows that even the macrocyclic GBCAs that were studied did leave gadolinium residues in the brain of patients that had many (over 20) injections.


This summary only reflects our side of the Atlantic. Europe, where a similar debate about GBCA safety risk occurred about gadolinium retention in the brain, concurrently to the one in the U.S., has taken a radically different stance on the issue. Following an extensive 17-month review of all available and unpublished research, a recommendation by the European PRAC (Pharmacovigilance Risk Assessment Committee) –the European equivalent to our U.S. FDA – was followed by an actionable decision by the CHMR (Committee for Medicinal Products for Human Use), to pull from the market all linear GBCAs, namely Bracco’s MultiHance, GE’s Omniscan, Bayer’s Magnevist, and Mallinckrodt’s (now Guerbet) OptiMARK.

On the Vendor Side: Wishful Thinking and Proactive Moves


Perhaps the most insightful part of the recent September 8,2017 Open Public Hearing 

of the FDA’s Medical Imaging Drugs Advisory Committee (MIDAC) was the timeslot allocated to the GBCA vendors. It is interesting to note that in this utmost situation of public health, the vendors did not reach a consensual opinion. Each vendor seemed to be taking the stance that best matches their own GBCA product(s) profile, based on their individual adoption level in the U.S. marketplace. This gave the perception of bias depending on whether their GBCA uses a closed-chain or macrocyclic (more stable) or open-chain or linear (less stable) chelate, and whether their product is profiled specifically in the clinical studies under evaluation, or not.

For example, GE Healthcare continues to argue that the benefits of administering a GBCA far outweigh any risks for Omniscan, which remains its dominant product in the U.S. and one that has been studied extensively. But at the same time, in Europe, GE is actively launching Clariscan, a macrocyclic and ionic (and therefore more stable and, presumably, safer) GBCA which they introduced at ECR 2017, with marketing authorization already in place, at least in Norway.

For Bayer, who operates two strong GBCA products in the U.S., one linear open chain and one macrocyclic closed chain, the position seemed naturally in evolution as their marketplace shifts from the linear to the macrocyclic.

As for Guerbet, who feels comforted by the presumably better stability and safety profile of its flagship macrocyclic GBCA Dotarem, it is acknowledging the fact that it is proactively phasing out from all markets the linear GBCA OptiMARK that came with its 2015 acquisition of Mallinckrodt’s contrast media and delivery systems (CMDS) business, independent of any decision in the U.S. about this product family.

People Moves: Awareness, Concern, and Angst


In this context of uncertainty, keeping abreast of a constantly growing body of scientific evidence, an engaged community decided not to wait and see what will come out of federal rulings from the FDA or other regulatory bodies. The web site 

 established by the Lighthouse Project has, since 2014, set out on its mission to “shed light on the effects of retained gadolinium from Contrast MRI”. In essence, here is a civic or social media movement that has taken ownership of an ostensibly medical issue, of which it wants the public more informed.


Big questions still remain unanswered. More ongoing clinical studies may soon unfold, with some possibly proving a causal link between gadolinium retention and various adverse secondary effects. This could be demonstrated even in healthy kidney patients and even in patients undergoing a not-so-high number of contrast-enhanced MRIs. Other studies, like the latest one out of Norway, may show that even macrocyclic GBCAs are not that much safer after all.

But while the controversy will probably not taper off anytime soon, can we contemplate a future without Gadolinium at all? This will require substantial validation and will take time, but a recent study published in 

shows promising works-in-progress towards a manganese-based contrast agent (MBCA) that could offer an equally effective but possibly much safer alternative to GBCAs.
 

Recent FDA review process of inconclusive clinical studies creates a potentially unhealthy decision-making environment for patients needing gadolinium-enhanced MRIs.

U.S. Patients Left Fending For Themselves with Gadolinium Safety Risks

It’s one of the perks of working out of Paris, France: to be living in one of the world’s capitals of art. When time is short, it’s hard to think of a better mental escape from work matters, than visiting a nice art exhibition.  I used to expect the world I work in – the medical imaging industry – would not intrude on that of my free time, in which beaux-arts getaways are supposed to offer a complete change of scene. Ironically, it happened a few times in the last two years that medical imaging matters just bluntly intruded on a few of these arty escapes.   I stumbled on this wall sculpture at the 2015 edition of the renowned Paris Art Fair. There, twice a year, the latest creations of hundreds of artists and designers are displayed in one of Paris’ most amazing venues, under the huge barrel-vaulted glass roof of the Grand Palais. [[{"type":"media","view_mode":"media_crop","fid":"57939","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_4105259646434","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7304","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 473px; width: 630px; float: right; margin: 1px;","title":" ","typeof":"foaf:Image"}}]]It took me a minute or so to realize, two hours into an inspiring art stroll, that the reason this strange form I was staring at looked familiar, was because it was actually a green-painted scanner gantry cover. It could be from a CT or an MR scanner, I still can’t tell, but the fact that it was elevated here as an object of art made me think that we, who work in the medical imaging field and see these machines every day, tend to forget sometimes what amazing pieces of design work these objects really are. A few months later, I found myself one day in the basement of the Fondation Cartier watching a video installation made on the occasion of a retrospective exhibition of Daido Moriyama’s work. He’s a contemporary Japanese photographer who, throughout his career, worked extensively on the topic of market consumerism. In this 10-minute film, random images were rolling on two large screens, meant to represent the mix-and-match of random sights and visual memories we experience in our daily lives.[[{"type":"media","view_mode":"media_crop","fid":"57940","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_2187328269079","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7305","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 473px; width: 631px; float: right; border-width: 0px; border-style: solid; margin: 1px;","title":" ","typeof":"foaf:Image"}}]] The picture I snapped caught the moment when an X-ray image came up right next to the brand of a mass-market drink, which also happens to be one of the major pop-art symbols of our consumer society. At a time when healthcare consumerism is becoming a big topic, this coincidence felt ironic indeed. This also made me reflect on the extent to which our medical images, which patients bring back home along with the “good news” or “bad news” of their diagnosis, can create a lasting visual memory in people’s minds. The art intrusion struck again recently, when I came across, in a museum, a series of photographs called Mein Gehirn (German for “My Brain”), work from the late 1980s of a German artist called Isa Genzken. A hospitalization episode led the artist into a creative process whereby she felt the urge to look “inside herself.” With this introspective work, Genzken reminds us how fascinating our medical images can appear to the untrained eye, as we all struggle to understand how our minds and bodies really function. She also makes it a point that medical images can very much be looked at, as the curator puts it, a “unique variation of the self-portrait.”[[{"type":"media","view_mode":"media_crop","fid":"57943","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_5956298627460","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7308","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 191px; width: 630px; float: right; border-width: 0px; border-style: solid; margin: 1px;","title":" ","typeof":"foaf:Image"}}]] Closing out with another sight of increased romance lately between medical imaging and art, this week I learned about a new visualization technology called “cinematic rendering” that looks like it could well be right there, at the intersection of the two. Its inventors, Siemens Healthineers, released the 

 created with the innovative algorithm. Geared right now at research, teaching, or at better physician-patient communication, the technology is “A Journey Inside the Human Body” that may, down the line, become a valuable interventional planning tool when it develops into clinical use cases. The novel rendering technique, inspired by the animation work that we’re used to coming out of the movie industry, produces medical images that look more “photorealistic” than ever before. As I contemplate these images, there are some I find so esthetical that it becomes hard to draw the line between where medical imaging stops, and where artistic imagery starts. But why try to force down that line, anyway?  [[{"type":"media","view_mode":"media_crop","fid":"57942","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_7481222734328","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7307","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 840px; width: 630px; float: right; border-width: 0px; border-style: solid; margin: 1px;","title":" ","typeof":"foaf:Image"}}]]Photo credit: healthcare.siemens.com

The beauty of medical imaging is easy to overlook, but it's still there. 

When Medical Imaging Meets Art

As we could glean from HIMSS17, seven major imaging and IT vendors are setting out to be the first to build and operationalize the next-generation cloud-based platform for advanced imaging analytics. The opportunity to become the ‘Android’ or the ‘Apple Store’ of imaging informatics – where providers can access and use a host of applications all from a single unified user interface, through non-capital intensive pricing models and independently of the hardware they use – is immense, indeed.  These large public or hybrid cloud platforms must compete against one another to attract value-adding content from the best-and-brightest independent software vendors (ISV) out there, to, in turn, deliver them as software-as-a-service (SaaS), likely through various flavors of subscription-based and pay-per-use models. These will serve to complement the vendors’ native applications to form a comprehensive and diversified portfolio. 

 - Siemens Healthineers Digital Ecosystem: Arguably, the most significant industry development for imaging informatics at HIMSS17 was the debut of the “Siemens Healthineers Digital Ecosystem.” The cloud-based 

 expands on the native teamplay portfolio which Siemens reported at RSNA 2016 was already operational at more than 160 sites. Now evolved into an ecosystem, it incorporates a variety of third-party apps for providers to choose from, ranging from advanced MRI (Arterys, SyntheticMR) to teleradiology (Second Opinions, USARad, TMC (Europe)), business analytics (Viewics, Dell-EMC) – among others and with more to come. The ecosystem appears to be quite mature and is expanding at a rapid pace globally, benefiting from the productive partnership of Siemens Healthineers with Microsoft Azure. As a case in point, the pair has even been able to ‘crack open’ the German market, notorious for its stringent data privacy laws and, arguably, the most difficult to penetrate with cloud solutions in healthcare. Siemens Healthineers may have made this introduction more than a year after its rival GE Healthcare soft-launched the GE Health Cloud, but the level of advancement and integration of the solution makes it anything but a “me-too” play for Siemens Healthineers, who seem to have operationalized the Digital Ecosystem quickly and robustly. This exciting, new development could not be timelier for Siemens Healthineers, as the company readies its spin-off later this year. - IBM Watson Imaging: HIMSS17 was quite significant on the imaging front for IBM Watson, as the company showcased its first market-ready native application: the Clinical Image Review application is the brainchild of the partnership IBM Watson entered with Memorial Sloan Kettering in 2012. Limited in its current use case to arterial stenosis, it is an un-regulated application that helps flag up discrepancies between medical imaging reports, in this case from echocardiography, and the related clinical notes in the medical records. This allows providers to recall at-risk patients who may have been discharged without the proper follow-up.  As such, in its current marketable form, the application works with imaging reports and not with the images themselves at the pixel level. The latter use case would more likely fall under IBM Watson’s regulated product line of applications, where project codename Avicenna belongs, and which is still demo’ed as work-in-progress.  Unfortunately from IBM Watson, this successful productization off of the Sloan Kettering partnership was somewhat over-shadowed during HIMSS17 by 

 about the much less successful outcomes, at least to-date, of the ongoing partnership with MD Anderson, Sloan Kettering’s oncology luminary rival. As far as building an open imaging analytics ecosystem, the company seems still somewhat shy of fully opening-up IBM Watson Imaging to third-party ISV’s applications. However, the integration of Medymatch’s deep learning application announced at RSNA 2016 is proof that IBM perceives the future of Watson Imaging as a platform – not just a home to its native applications. - GE Health Cloud: Now well into its second year since it was announced at the RSNA 2015, the operationalization of the GE Health Cloud is still advancing, with good progress so far in the U.S. and the UK markets. However, it is fair to note  the GE Health Cloud momentum, as it transpired from RSNA 2016 and HIMSS17, is nowhere near that of its debut a year when the ecosystem seemed to be 

 at record speed. Indeed, although it is part of the corporate-wide ‘Industrial Internet’ initiative of GE, the Health Cloud is evolving at its own pace due to healthcare-specific regulations. Working with cloud partners Microsoft Azure and Amazon Web services (AWS), GE Healthcare is phasing out the Health Cloud incrementally, country by country. 

Two Contending (and Complementary?) Runner-Ups

 - NTT Data: The new owner of Dell Services, which include the legacy of InSiteOne, the industry pioneer for cloud-based medical image archiving, is in a somewhat good position to become one of the go-forward medical imaging analytics ecosystems. Already, at the time of the NTT Data acquisition, the Unified Clinical Archive (UCA) had started to grow into a managed cloud-based platform featuring several value-adding analytics applications, notably from medical imaging deep learning experts Zebra Medical Vision and Imbio. Now, NTT Data wants to leverage the UCA to grow the company’s presence in the North American marketplace. But, for this to happen – and despite being very well-known across Asia – it  will be crucial for NTT Data to build its footprint and brand name stateside. - Philips Healthcare: The enterprise imaging developments of Philips Healthcare are quite impressive, notably how the company is able to bring together the full imaging IT solution suite into a unified platform under a unique, managed services model. On the other side of the house, the Philips HealthSuite cloud solutions are advancing steadily, as well, yet it is still focused mainly outside of the acute care setting and in support of Philips’s care continuum strategy. These two pillars of healthcare informatics at Philips are yet to converge, to create what can be deemed a cloud-based medical ecosystem from Philips. Perhaps, it will be along these lines that Philips Healthcare will make 

its next major partnership or acquisition.

 - Google: On the busy HIMSS17 booth of Google, the cognitive giant exhibited imaging-related works-in-progress from two distinct sides of the house. Google Brain on one hand, and Google DeepMind on the other, each showed their latest advances in computer vision applied to medical images, notably in the field of ophthalmology. The algorithm 

 can automatically detect diabetic retinopathy in retinal fundus images, while 

 can provide early detection of age-related macular degeneration from optical coherence tomography (OCT) images.  Eye imaging may well be the first of many more clinical applications to come from Google, and perhaps an ideal area pilot its cutting-edge computer vision methods given the wide global availability of eye fundus and OCT imaging. Indeed, Google Brain, for example, is already active in other areas, such as radiotherapy planning. Most certainly, these recent developments at Google mark a decisive re-entry of Google into the health arena, after it chose to discontinue its Google Health offering years ago. - Amazon: Coincidentally – or maybe not –, eye disease is also the area where Amazon chose to jumpstart its own machine learning medical imaging applications. Similar to Google’s, Amazon’s GPU-based 

 running in the Amazon EC2 cloud can automatically detect diabetic retinopathy from fundus images. This project may still be investigational and niche, but the fact is, Amazon is already extensively called upon to help cloud-enable medical imaging applications from its various partners through Amazon Web Services. Therefore, it is only a matter of timing before Amazon decides to promote its own cloud platform hosting a larger suite of native and partner applications. 

Major Vendors Seek Early-Mover Advantage in Operationalizing Advanced Cloud-Based Imaging Informatics Platforms

HIMSS17: The Race for Medical Imaging Analytics Ecosystems is Open

The medical imaging and informatics industry seems to be about to embark on another big wave of financial transactions from varied initial public offerings (IPOs), spinoff, and merger and acquisition (M&A) activity. Eleven RSNA Annual Meetings that I have attended in a row may or may not be enough to judge, but the last time M&A seemed so intense to me was in the mid-2000s, when almost every major radiology PACS vendor picked up a cardiology PACS vendor.

Without us getting into any speculation or financial advisory, there are a few high-profile vendor moves that are undergoing, planned or expected to occur over the next few months, that will make 2017 an interesting year to watch unfold:

When Siemens AG, the parent company of Siemens Healthineers, officially announced the $50 billion spin-off plan of the health care group, 

. This suggests that the investment community may have perceived the carve-out of the health care division as alleviating the German industrial giant of a weighty asset. The hypothesis goes that Siemens AG is anticipating major growth impetus when the contracts kick in to rebuild the U.S. infrastructure under Trump’s America. The outlook for the health care industry, however, is more uncertain. In the best-case, it will continue to grow slowly, and in any case, it will continue to be shaken by macro-economic forces.

The rationale for the spin-off, then, is to create a new ownership structure for a company dedicated to health care that can decide and execute its own growth plan more autonomously. By all accounts, Siemens Healthineers has long been and remains 

 technology leader in the medical imaging industry. Realizing its growth potential will certainly benefit from higher flexibility in its governance.

The latest in a long history of spinoffs, this carve-out of the Imaging Components segment of Varian Medical will be an independent company and 

. The new company’s executives, who come from Varian, confirmed at the investor meeting held at RNSA that the transaction should be completed in early 2017. The soon-to-be stand-alone company kicked off 2017 with a bang, by 

acquiring the medical imaging assets of PerkinElmer

, one of its main competitors, and the supplier of components to GE Healthcare, for one.

Historically, Varian Medical has always held a strong to very strong position across the value chain of X-ray imaging - from static and dynamic X-ray tubes, to flat panel detectors, to image processing. More often than we think, it is the component manufacturers that are the real innovators behind the latest product innovations of the large system integrators. The hope is that by operating as an independent company, Varex Imaging will be better able to stay at the leading edge of technology innovation, to continue to strengthen its value-add to OEM customers, to expand its market access, albeit while fighting price pressure and commoditization in some of its product areas.

, Change Healthcare will become the new umbrella for McKesson’s health IT and imaging IT business lines.  The Blackstone Group, majority owner of Change Healthcare, said it would likely launch an IPO in the months following the transaction. While McKesson continues to be strong in imaging informatics, that is not the case for every other area of its health IT initiatives. The synergies with former Emdeon, which constitutes the ‘other half’ of Change Healthcare, should be interesting to watch.[[{"type":"media","view_mode":"media_crop","fid":"56056","attributes":{"alt":"Nadim Michel Daher, Industry Principal, Medical Imaging and Imaging Informatics, Frost & Sullivan","class":"media-image media-image-right","id":"media_crop_2863155644610","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7038","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 250px; width: 200px; border-width: 0px; border-style: solid; margin: 1px; float: right;","title":"Nadim Michel Daher, Industry Principal, Medical Imaging and Imaging Informatics, Frost & Sullivan","typeof":"foaf:Image"}}]]

• Agfa-Gevaert, the parent of Agfa HealthCare: 

 As soon as German hospital IT vendor CompuGroup Medical made public its 

 Agfa, the stock price of Agfa went up by double-digits. This reaction of the financial market makes sense, because there is every reason to believe that CompuGroup, as a pure-play health IT player, is really only interested in the assets of Agfa that are 1) health care and 2) digital. The legacy businesses of Agfa Gevaert, such as the analog and graphics divisions, may continue to be profitable, but are likely not the type that any entrepreneurial investor betting on health IT or medical imaging would want to go after. The CompuGroup attempt rapidly turned out inconclusive 

. However, it hints at the scenario of a “hostile takeover” of Agfa Healthcare from Agfa Gevaert, which may interest more investors.

Shortly after its ten-year investor owner, Onex Corp officially put it up for sale, rumors surfaced the sell-off would involve a 

 of the Carestream Health organization. This means the company, valued at more than $3 billion, could see its digital X-ray, film, imaging IT, dental, and ultrasound divisions take different directions. This idea of ‘piecemealing’ Carestream Health to different investors has somewhat of a sad spin to it, because since the Kodak days, the company has managed to balance well the cycles of success and slowdown in each segment.

Until today, Carestream manages to remain very innovative on numerous fronts of its portfolio. However, it may well be time for Onex to take a serious pulse check at the remaining synergies – or actually the lack thereof – between the different business lines of Carestream. Is radiography equipment still driving the PACS business, or vice versa? Is there still any overlap left between digital imaging and analog film operations? Is dental going to become any less of a world of its own in the new health care environment?


How valuable is the imaging IT business of Carestream alone, for example, considering that IBM paid no less than $1 billion for Merge Healthcare a year ago? Merge’s global imaging IT footprint is smaller than Carestream’s, which leads the large-cloud PACS market in dozens of countries. If a potential investor is really looking to capitalize on the goldmine that lies in these big medical imaging datasets, there is no reason why Onex would not expect a seven-digit valuation for the Carestream imaging IT business alone.

Each of Change Healthcare, the Agfa-CompuGroup combination (if the takeover had occurred), and Carestream Health (if it gets sold as one asset) represents roughly $3 billion of annual revenue. Three-billion-dollar-sized companies seems to be a sweet spot for the health care industry today –not too small, so as to still have credibility and access to ‘big-fish’ contracts, but not too big either, so as to be able to maintain the entrepreneurial as well as an intra-preneurial spirit required by the changing health care environment.

Big ticket deals for prospective investors on the RSNA 2016 showfloor.

2017’s Investment Opportunities in Imaging and Informatics

The life sciences field is inching closer each year into the era of Theranostics. The word sounds fancy, but, fortunately, its definition is simple. Theranostics stands for the integration of therapeutics and diagnostics. The promise of theranostics is huge: every step forward in this direction is also a step into the future of medicine – a medicine that is more predictive, translational, personalized, and precise than the one we practice today.

Theranostics is an up-and-coming field that only few innovative pharmaceutical companies can claim to be fully active in today. With new generations of in vitro diagnostics, molecular therapeutics or biosensors coming of age, we are getting closer to having ‘smart’ drugs that can detect diseased cells, attach to these cells, and then destroy them, providing end-to-end treatments for oncology or neurology. This begs the question, what’s in it for medical imaging?

Cross-Pollination and Synergies Between Pharma and Imaging


	The fact that the life sciences field is top-of-mind in the area of theranostics doesn’t mean there is no place for imaging in this field; on the contrary. In fact, the cross-pollination between imaging advances and these ‘smart’ drugs are already a reality in the research realm, where they are seen as two synergistic levers for theranostics.

: The ongoing advances in molecular imaging, which today allow visualizing form and function at once and more precisely than ever before, are of tremendous help in the discovery and clinical trial phases for new drug developments.

: Similarly, the advances in contrast agents for X-ray or magnetic resonance imaging, radiotracers in nuclear medicine, or microbubbles in ultrasound, are helping make the drugs smarter in how they can recognize and bind to their target cells.

It should come as no surprise that we start to hear the word “Theranostics” at the medical imaging tradeshows, such as RSNA, particularly on the part of nuclear imaging industry participants. Siemens Healthineers, for example, showed several imaging advances that are very relevant in the context of theranostics, including continued advances in SPECT quantification, and an extended spectrum of radiopharmaceuticals supported by its quantification software, beyond the four most widely used ones.


	Ultrasound, the modality that never ceases to push its limits and reinvent itself, is one amazing testbed for diagnostic and therapy integration. The new generation of wireless transducers can be almost embedded into a big-iron modality’s gantry for image guidance. Another convergence is in the brand new range of therapeutic focused ultrasound systems from various vendors and in various applications, such as MR-guided focused ultrasound. In the end, the difference between the diagnostic and therapeutic families of ultrasound products is a matter of beamforming and wave strength. As with X-ray, one can already see the signs of the two getting into grey territory.

High-Energy and Low-Energy X-Ray: Ambiguously Separated Industries[[{"type":"media","view_mode":"media_crop","fid":"55252","attributes":{"alt":"Nadim Michel Daher, Industry Principal, Medical Imaging and Imaging Informatics, Frost & Sullivan","class":"media-image media-image-right","id":"media_crop_1165283876582","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"6906","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 250px; width: 200px; border-width: 0px; border-style: solid; margin: 1px; float: right;","title":"Nadim Michel Daher, Industry Principal, Medical Imaging and Imaging Informatics, Frost & Sullivan","typeof":"foaf:Image"}}]]


	On the X-ray industry side, the radiation therapy field on one hand, and diagnostic/interventional imaging on the other hand, each have its own set of industry giants. The manufacturers of linear accelerators – Varian, Elekta, Accuray, etc. – and their counterparts in imaging – GE Healthcare, Siemens Healthineers, Philips Healthcare, etc.- today address largely separate market opportunities, respectively for treatment and diagnosis, respectively.

Both groups work with X-ray beams, but in very different ways. The first group is tasked with delivering a high-energy X-ray beam that is so thin and so focused that it can destroy diseased tissue without any harm to healthy surrounding tissue. The second group’s systems deliver a low-energy X-ray beam that is so diffuse and even that it can image disease without over-radiating patients. Therefore, the components and engineering processes are very different across these two industries, however, collaboration and integration between the two has been going on for many decades, and has taken a whole new turn over the last five years.

Integrated MR-Linac for Real-Time Image-Guided Therapy


	The current state of the art in radiation therapy relies on images acquired prior to the actual treatment, which are used at the treatment planning phase. This means they cannot take into account organ movement during treatment. This is obviously less than ideal for precision. Imaging comes in again post-treatment, for response assessment. This means patients undergo multiple different procedures, each with its own experts, equipment, cost, and workflow. In the context of value-based care, there is a strong rationale for marrying the core competencies of radiotherapy and imaging vendors into one, integrated system.

This is exactly the concept that ViewRay has developed with its MRIdian system, an industry-first, integrated MR-linac (0.35 Tesla) system that has been FDA-approved since 2012. Installed in four U.S., one Netherlands, and one Korean location as of 2016, the system has been in clinical use since 2014 and treats more than 15 patients a day at Washington University in Saint Louis. Two similar developments, which are still investigational, are underway at the Cross Cancer Institute in Canada and the University of Sydney in Australia. It is in this competitive landscape that Philips and Elekta have step foot, with a high-field (1.5 Tesla) integrated MR-linac system. This represents a true industry breakthrough.


	In 2012, the two vendors established a consortium led by Elekta, with Philips as the partner for MRI, and prototyped the system together with their clinical partner at the University Medical Center Utrecht (UMCU) in the Netherlands, where a second unit was installed in 2014. The MD Anderson Cancer Center in Houston installed their own in 2015. In what appears to be an exponential turn, a number of additional clinical consortium partners have initiated or completed their installation in 2016 across the Netherlands, the UK, Canada, and the U.S. The stars seem aligned for the Philips-Elekta partnership to be the beginning of a huge success story: the new installations and order backlog are on a roll; the body of clinical publications are building up in the global academic community.

Philips Healthcare still has a considerable amount of cash on hand since the spin-off of the Lighting division, and despite the $1.2 billion acquisition of Volcano therapeutics in the very end of 2014 – the integration of which is proving very successful.  My own personal prediction as an analyst is, the day Philips has clarity on the FDA timeline for the new MR-linac, Philips will move ahead to acquire Elekta.

RSNA 2016 displays more signs pointing towards the blending of diagnostic, interventional, and therapeutic imaging.

RSNA 2016: Baby Steps for Theranostics in Imaging 

The Windy City wasn't at all windy this year, not even cold or snowy for that matter, but RSNA-goers could feel the winds of change blow on the McCormick technical exhibits floor. The transformation of the medical imaging industry is wide and deep, especially in the re-organization of the big vendors.

Informatics + Services as a Recipe for Value Creation


As part of an ongoing trend of the last several years, imaging informatics continued to claim an ever higher footprint of the RSNA 2016 showfloor. Imaging informatics solutions, as providers already know well, provide cost-effective ways of getting more value out of capital imaging equipment investments. They are essential in helping expand imaging service lines or the reach of imaging services, and the efficiency of both. Now, informatics is joined in this momentum by professional value-adding services. The parallel between the Big Three medical imaging vendors is striking. For each of GE Healthcare, Siemens Healthineers, and Philips Healthcare, imaging informatics and professional services have never stood as close to one another before. While the synergies between the two business lines have always existed, in 2016 we can start talking about real, game-changing convergence.[[{"type":"media","view_mode":"media_crop","fid":"54955","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_1861679419818","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"6879","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 200px; width: 200px; border-width: 0px; border-style: solid; margin: 1px; float: right;","title":"In the Philips Healthcare booth, the section highlighting the latest additions to the enterprise imaging IT portfolio (IntelliSpace Portal 9.0, Universal Data Manager, Illumeo), was the same section where PerformanceBridge software and services were demonstrated.","typeof":"foaf:Image"}}]]

This convergence of imaging informatics and professional services is probably least of a novelty in the case of Philips. In the U.S., this can be dated back to the launch of its “Healthcare Transformation Services” consulting practice in 2013. In addition, the vendor has, at least in the U.S. market, a stronger legacy of managed imaging IT services compared to its two top competitors. In radiology PACS for example, Philips has pursued this deployment model in a significant portion of its installed base ever since the acquisition of Stentor in 2005. Similarly on the equipment side, the vendor has been enjoying an early-mover advantage with regard to large-scale managed equipment services (MES) models. There is not one corner of the globe where Philips has not yet engaged with hospital chains into long-term MES-type partnerships, with contracts valued in the tens, if not hundreds of millions.

The Informatics and Services Pair at Center Stage of Booth Design


RSNA 2016 marks the year when Philips made significant additional steps in this direction, notably with the launch of PerformanceBridge, a new suite of performance management software and services.  The ‘Powered by HealthSuite’ label means the health care cloud strategy of Philips, which made its initial steps outside of the acute care setting, now has a solid entry into radiology. It also shows Philips has been able to ‘productize’ around its advisory and analytics services, which have been the cornerstone of its large managed services contracts.

For both Siemens and GE, however, the convergence of informatics and services is more recent, and no less than transformational for these two vendors who dominate the U.S. market from a modality sales volume standpoint.

Enter the Transformation of Siemens Healthineers and GE Healthcare


Siemens has been quite interesting to watch it restructure the organization of its professional services arm throughout 2016. This massive endeavor has been taking place concurrently with the re-branding effort from “Healthcare” to “Healthineers”, which shows the extent to which the new services structure is very much inherent to the future that Siemens Healthineers sees for itself as a stand-alone health care company. Siemens can now articulate very elegantly its value proposition around three service pillars. “Customer Services” keep the lights on for its customers; no major change on that front. The “Digital Services” segment, however, now groups the imaging informatics portfolio together with several value-adding services, while the “Enterprise Services” line is tasked to develop the two into new business models such as multi-vendor and managed services.

Along the same lines, GE Healthcare's “Digital Health Services” and GE Digital’s “Customer Success Services” lines leverage informatics solutions in a big way. The latter range provides a range of advisory, managed, implementation, and education services that, take advantage of the Predix Internet of Things approach, which is originally industry-agnostic, and applying it to medical equipment and health care. These are some of the tools that are now in the hands of GE’s sales organization, from regular account managers to GE Healthcare Partners for strategic accounts, to elevate the company from selling ‘boxes’ and associated services, to selling ‘solutions’, to selling ‘outcomes’. By ramping up the value proposition to the C-suite, partly through the acquisition of the Camden Group in November 2015, 2016 marks a turning point for GE Healthcare’s market strategy.

Analytics-as-a-Service: A Lever for Services and Door Opener to the C-Suite


This transformation of the Big Three is actually dictated by the changes in their customer bases. By some accounts, the seemingly unstoppable consolidation in the U.S. health care provider market will soon leave no more than 600 institutional purchasing entities (integrated delivery networks, health systems, etc.) to sell into on the hospital side. It is also safe to assume that capital purchase decisions for medical imaging equipment in these increasingly large entities will be made to a large extent in the highest management spheres. And to the nonclinical stakeholders among them, their interest is more on the side of managing and optimizing their capital assets and fleets, than in the bells and whistles of imaging equipment.

In this context, the convergence of informatics and services means a lot more to the vendors than merely developing a stronger play in IT-as-a-service. Analytics-as-a-service, for instance, is a crucial internal asset for them to position as partners to their customers in helping them deliver value-based care. Indeed, as their influence on capital investments continues to grow, C-level decision-makers are demanding a stronger tie-in between their imaging investments and the institutional outcomes that determine their financial risk and value-based payments under accountable care organizations. In the customer-centric sales approach that they are now developing beyond their “key accounts” and the limits of their own installed bases, modality equipment sales-people only come in as second-line to account managers and advisors, and multi-vendor service (MVS) neutrality is crucial.

Imaging Analytics Dashboards: the Vendor Race is On


GE Healthcare’s build-up in the breadth and depth of the operational, financial, and clinical modules in the GE Health Cloud powered by Predix, is quite impressive to say the least. Reportedly, the nine in-house modules pertaining to radiology that GE demoed at RSNA 2016 are mature and ready-to-market. GE’s openness to engage with third-party independent software vendors contrasts with Siemens’s approach, which prides itself on building 

 onto a single, in-house developed platform. Given its freemium model and easy deployment through the Microsoft Azure cloud, 

is shaping up nicely as well as it continues to gain global footprint.

More than 400 accountable care organizations (ACO’s) are taking on financial risk, passing it on to providers who, in turn, are engaging radiology under shared-risk contracts. Accountable care is trickling down to what can be dubbed ‘accountable imaging’. As this happens, there is no doubt that the analytics capabilities of imaging equipment vendors, and the value-adding services that stem from them, will become more and more of a differentiating factor in the competitive race.

The focus of the big three vendors at RSNA 2016.

RSNA 2016: Coming as One for Imaging Informatics and Services

Much is said about cardiac SPECT imaging programs becoming less reliable because of challenges in the global supply chain of Molybdenum-99, the parent nucleus of Technetium-99. Reinforcing the pessimistic outlook is the fact that a new shortage of Technetium-99, the main cardiac SPECT radiopharmaceutical, seems to be looming on the nuclear cardiology marketplace, similar to the last major one from 2009-2010.

The planned shutdown on March 31, 2018 of the NRU nuclear reactor of Chalk River in Canada – anecdotally the world’s longest-operating, with 60 years in the running – is reviving worries of market unavailability and price volatility of these agents, and steering some cardiac SPECT providers to take a closer look, again, at cardiac PET for myocardial perfusion imaging procedures.

Will the projected Technetium shortages be a

Perhaps, but one must keep in mind the Rubidium supply chain is not much more diversified. The degree of industry concentration, and the dependence on a fairly limited number of actors in the supply chain, are just as high for Strontium-82, the parent nucleus of Rubidium-82, as they are with Molybdenum-99. Indeed a comparable number of accelerators is available globally to produce, as a small part of their diversified production, Strontium-82 for the medical industry. Namely, these are Brookaven National Laboratory (BNL) and Los Alamos National Laboratory (LANL) in the U.S., iThemba labs in South Africa, INR in Russia, Triumf in Canada, and Arronax in France.

However, the industry concentration in source supply may diminish, if many new commercial cyclotron providers see the light.  In September 2015, Indiana-based Zevacor Molecular announced it had installed the first strontium-82 cyclotron in the U.S., manufactured in Belgium by Ion Beam Applications, who was awarded the contract in 2013. As of this day, the company has not publicly announced a launch of commercial production.

Bracco Diagnostics: 28 Years of Owning the Rubidium Generator Market


As the first company to invest heavily in cardiac PET MPI, Bracco has been, since 1989, the only company with an FDA-approved generator-based perfusion agent available for cardiac PET: CardioGen-82 (Rubidium-82). Starting in 2017, however, Bracco will have to face a newcomer to the U.S. Rubidium-82 scene: Jubilant DraxImage. The next few years will tell whether this represents a new competitive threat for Bracco, or a new opportunity for cardiac PET’s market growth.[[{"type":"media","view_mode":"media_crop","fid":"52738","attributes":{"alt":"Nadim Michel Daher, Industry Principal, Medical Imaging and Imaging Informatics, Frost & Sullivan","class":"media-image media-image-right","id":"media_crop_1895907038546","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"6549","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 250px; width: 200px; border-width: 0px; border-style: solid; margin: 1px; float: right;","title":"Nadim Michel Daher, Industry Principal, Medical Imaging and Imaging Informatics, Frost & Sullivan","typeof":"foaf:Image"}}]]

Today, the uncontested leadership position the Bracco organization has built over almost three decades puts the company in an ideal position to focus on addressing the challenges intrinsic to the cardiac PET supply chain, and breaking some of the barriers to adoption that still exist. The company continues its work to enhance the distribution network, contain operational costs, simplify the logistics, sponsor clinical research, and provide training to a gradually growing population of cardiac PET providers.


The latest breaking-news came days after the ASNC 2016 meeting wrapped up: the FDA has approved Jubilant DraxImage’s RUBY-FILL complete generator-elution system for PET MPI (October 2016). This is a major industry development for the U.S. market, where Bracco’s single-vendor play was perceived by some as a “monopoly.” This FDA nod practically signals the advent of a new “generic” version of CardioGen-82 in the U.S., which will likely provide a competitive and cost-effective option to the cardiac PET market.

In its Canadian home market, the Rubidium -82 generator has already obtained Health Canada approval for clinical use, however the associated elution system, which in Canada is looked at separately, is not yet approved for use. “ARMI” and “REST-PET”, two ongoing clinical trials of the company, as well as the latest U.S. FDA approval, may help accelerate the path of RUBY-FILL towards commercial availability in Canada.

Ionetix: Ammonia Cyclotrons for High Volume Facilities?


In February 2016, Ionetix was the first vendor to announce it had produced doses of N-13 Ammonia for clinical use, in its new University of Michigan Health System cyclotron. The N-13 Ammonia radiopharmaceutical performs well compared to Rubidium-82 but has a radically different operational model. It has a 10-minute half-life and can only be produced in a nearby cyclotron, compared to Rubidium-82 which has a shorter half-life of 70 seconds, but can be produced using a much less expensive on-site generator.

These logistic constraints mean that N13 Ammonia has very high start-up costs that could fall in $1 million territory, followed by relatively low fixed costs for the production of clinical doses. In contrast to Rubidium-82, which offers low start-up costs but high ongoing costs upwards of $30,000 per month for the replacement of on-site generators, it is clear that N13 Ammonia can only be financially viable for high-volume facilities. Therefore, Ionetix needs to experiment with alternative business models, possibly around managed equipment services, to be able to break into the market.

Lantheus Medical Imaging: Active F-18 Investments to Deliver Soon?


In May 2015, Lantheus Holdings, Inc. announced the results of the first of two phase III trials for the flurpiridaz F-18 PET MPI agent it has under investigation. Currently, the company is preparing to commence the second phase III trial, which it plans to conduct through partnership. Like every other imaging technique, F-18 is differentiated with some powerful, but perhaps also some limiting attributes. On the upside, F-18 has a half-life of 110 minutes, appears to perform extremely well on obese patients, have high sensitivity compared to the SPECT MRI, and improve on absolute quantification of myocardial blood flow (MBR) compared to Rubidium-82 PET. The latest trial results have shown flurpiridaz F-18 to be compatible with exercise-stress testing, and not entirely dependent on pharmacologic stress-testing (eg, with adenosine, dipyridamole [Persantine], or dobutamine).

On the flipside, given Lantheus and its prospective partner would most likely be the first to enter the market with a flurpiridaz F-18 agent, they will probably need to implement a brand new operational and commercialization model for the new agent, once it is ready to enter the marketplace.

Latest developments in cardiac PET radiopharmaceuticals from ASNC 2016.

Technetium Shortages Loom, Dynamics Heat Up in PET Perfusion Agents


Cardiac PET is, objectively, one of the most powerful imaging modalities in functional imaging of the heart. It is able to image cardiac function and blood flow non-invasively with higher sensitivity and/or specificity than many competing imaging technologies. Higher diagnostic accuracy, better image quality, shorter overall procedure times, lower dose, more robust quantitation, less dependence on patient size – are some of the attributes where cardiac PET often shines in the inter-modality race.

At least on the tech-specs front, perfusion imaging of the heart with PET can be deemed superior to well-established modalities such as cardiac SPECT, cardiac MRI, or stress echocardiography. This is the first-and-foremost ‘headwind’ that has enabled a fairly successful initial take-off for cardiac PET throughout the 1990s.


The problem with this technical roll of honor for cardiac PET, is it has been the ‘next big thing’ for almost three decades now. The initial take-off can be dated back to a major industry event in 1989, when Bracco Diagnostics’ CardioGen-82 Rubidium generator became the first FDA-approved radioimaging agent dedicated to cardiac PET. Or, the take-off can be dated back to 1995, when myocardial PET perfusion imaging (PET MPI) first gained approval for Medicare reimbursement.

Looking back just one decade, when I started as a medical imaging market analyst, many in the industry would sound very confident predicting that the utilization of cardiac PET was about to explode, and that if it did, this would finally give justice to its technical edge. Yet, today, ten years later, the tech-specs of cardiac PET look even better on paper, notably with the ability to measure coronary flow reserve (CFR) quantitatively, but the ‘explosion’ in its clinical use still hasn’t happened.

Utilization Stuck in the Low-Single-Digits


The few hundred early adopters of cardiac PET, both on the hospital as well as on the ambulatory side, have remained for the most part faithful to this cutting-edge modality – even through the voluntary recall of CardioGen-82 in 2011. While this healthy take-off could have edged up like a hockey-stick, only few more nuclear imaging, radiology, or cardiology service lines have since then jumped on the cardiac PET bandwagon.

The growth phase that would lead cardiac PET closer to adoption by an early majority of cardiac imaging providers, clearly has not yet materialized. Cardiac PET in the U.S. still represents merely around 2% of the volume of cardiac imaging procedures (well behind echocardiography, cardiac SPECT, cardiac angiography, among others), and around 5% of overall PET procedure volumes (still largely dominated by FDG imaging in oncology).

Reimbursement Stability, Following Record Fluctuations


Since gaining CMS approval in 1995, the reimbursement rates for PET MPI, the most prominent procedure, have varied widely. Most notably, a big jump in 2006 increased rates more than three-fold to above the $2,000 mark. Since then, a number of year-over-year cuts (e.g., minus 23% in 2011), billing code ‘packagings’ (eg, bundling of stress/rest imaging), and occasional increases (eg, +24% in 2010), have kept the rates on a rollercoaster ride.

Yet, PET MPI reimbursement seems to have stabilized over the last few years, around the $1,300 mark in the hospital setting, inclusive of around $250 for the radio-agent dose (Rubidium 82 or N-13 Ammonia). Comparing that to a reimbursement rate of about $1,200 for SPECT MPI, including one or two $70 Tc-99 doses, the financial model for PET MPI does not seem extremely bright.[[{"type":"media","view_mode":"media_crop","fid":"52574","attributes":{"alt":"Nadim Michel Daher, Industry Principal, Medical Imaging and Imaging Informatics, Frost & Sullivan","class":"media-image media-image-right","id":"media_crop_7828119449113","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"6526","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 250px; width: 200px; border-width: 0px; border-style: solid; margin: 1px; float: right;","title":"Nadim Michel Daher, Industry Principal, Medical Imaging and Imaging Informatics, Frost & Sullivan","typeof":"foaf:Image"}}]]

Business Case Viable only at Very High Patient Volumes


Despite being fairly well reimbursed, the payment levels are often not sufficient to offset the high costs of running a cardiac PET program. Purchasing a new rubidium tracer generator every 28 days can cost upwards of $400,000 per year, while investing in an institutional cyclotron is a large capital project that can fall well into the seven-digits. In addition to these high recurring or start-up costs, one must also factor-in the cost of block-scheduling ‘time slots’ from oncology or radiology on the PET-CT equipment, or the purchase of a stand-alone PET or mobile PET service.

Therefore, all in all, a cardiac PET imaging program is only able to break-even financially if it sustains a throughput of at least seven or eight patients a day. Today the demand is simply not there to sustain such levels, except at the very top segments of the market, such as large academic centers or cardiac centers of excellence.

Appropriate Use the Societies’ Number One Priority


As was clear from the 2016 annual meeting of the American Society of Nuclear Cardiology (ASNC)in Boca Raton, Florida, establishing standard appropriate use criteria (AUC) for cardiac PET is currently one of the society’s top priorities. As we prepare for the rollout of the Protecting Access to Medicare Act of 2014, this cannot be timelier. After acting somewhat protective of SPECT in the past, the ASNC is now working closer than ever with the Society of Nuclear Medicine and Molecular Imaging, which for its part has embraced PET since its inception. The two clinical authorities (respectively for nuclear cardiology and nuclear medicine) are now hand-in-hand in designing new cardiology care pathways and clinical protocols that seek to make the most appropriate use of the state-of-the-art molecular imaging armamentarium.

Based on the work-in-progress, it appears that provided a facility has access to PET, new protocols may deem cardiac PET most ‘appropriate’ for specific patient cohorts. For example, patients who are likely to have significant attenuation artifacts in SPECT, such as large patients and women with dense breasts. Specifically, PET MPI stands a high chance of being recommended, even as a first-line modality, anytime the primary goal of the pathway is risk stratification or viability assessment. The guidelines will capitalize on the modality’s unique capabilities to provide absolute myocardial blood flow quantification, as well as the evaluation of different forms of cardiomyopathy.

Bundled Payments and Turf Battles on the Short Horizon


Looking at the Bundled Payments for Care Improvement (BPCI) initiative of CMS, 14 out of 48 episodes of care where work is being done to develop a bundled payment pertain to cardiovascular care episodes. Like has already been implemented in orthopedics for hip-and-knee replacement under the Comprehensive Care for Joint Replacement Model, new Medicare payment bundles are underway in cardiology, notably one for coronary artery bypass graft surgery (CABG) and another one for acute myocardial infarction/percutaneous coronary intervention (AMI/PCI).

Adding to the mix of disruptive changes is the ongoing consolidation in the provider landscape, notably hospital acquisitions of nuclear outpatient labs and cardiology private practices, which in most cases tend to reorganize nuclear medicine under radiology. This, together with the adoption of hybrid imaging in general, is blurring the lines between molecular imaging and diagnostic imaging service lines.


These changes raise new, important questions that will shape out the future growth path for cardiac PET:

- Will the modality keep up with the ongoing advances on the cardiac SPECT front, notably the high-end tier of solid-state-detector cameras (GE Healthcare, Digirad, Spectrum Dynamics)?  

- Will it prosper as a constituent of the upcoming bundled care pathways despite its high cost, complex logistics, acute training, and spotty access?

- If it does pick up in a big way, who of radiology, cardiology or nuclear medicine departments will be best positioned to gain ownership?

American Society of Nuclear Cardiology 2016 shows the cardiac PET value chain still faces more headwinds than tailwinds.