Mina S. Makary, MD

 A previous version of this article cited a source that incorrectly indicated that the ICM shortage may persist through June 2023. GE Healthcare has refuted this claim and has confirmed as of June 14, 2022 that the company's Shanghai plant in China returned to full production capacity on June 8, 2022.

The global shortage of iodinated contrast media (ICM) has forced hospitals and providers to triage patients, reduce imaging utilization, switch imaging modalities, and postpone imaging studies. Effective strategies to blunt the impact of the ICM shortage are urgently needed as this crisis continues to have a profound impact on patients and health-care systems.

Like many other modern-day crises, the ICM shortage originated from the COVID-19 pandemic. A large percentage of the world’s ICM supply is manufactured in Shanghai, China. Strict pandemic lockdowns led to a near total cessation of manufacturing and shipment of the contrast media out of the country, which led to widespread shortages across the world. Although the Shanghai factory is now back to full operation, some imaging facilities may continue to have challenges with shortages until their supplies of ICM are restored to optimal levels.

Given this risk, it is prudent to develop and implement strategies that can effectively minimize the impact of the ICM shortage while maintaining high quality patient care. Multiple societies have put forward recommendations involving possible solutions, including triaging patients, using alternative imaging modalities, using alternative contrast agents, reducing overall imaging utilization, and creating central command structures.

One of the simplest but also most challenging of the recommended strategies involves changing what imaging tests are done and when. This can be achieved through triaging and delaying elective imaging. Triaging involves the difficult task of assigning a priority to each patient’s contrast needs. Keefe and colleagues proposed a three-category triage tier list, which includes emergent, delay for one month, and delay for three months.

 This novel strategy enables clinicians to ensure that patients with emergent needs are served quickly while also enabling health-care systems to extend their limited supplies until the crisis abates.

Another widely suggested remedy is the use of alternative imaging modalities. Possible alternatives include magnetic resonance imaging (MRI), ultrasound, and non-contrast computed tomography (CT) studies. Given the large overlap between MRI and contrast CT indications, increasing the use of MRI during this crisis has been broadly recommended.

However, there are limitations to this substitution. The primary impediments are the limited number of MRI scanners, their relatively higher cost, and the nature of the pathology. One solution to this is the use of “focused” protocols that minimize overall MRI time, which can enable each scanner to serve a larger number of patients with appropriate disease conditions.

Using alternative contrast agents is another frequently prescribed solution to this problem. Multiple alternatives, including carbon dioxide (CO2) and gadolinium, have been suggested, particularly when it comes to interventional radiology.

 Each of these substitutes has benefits and drawbacks that must be carefully considered.

Using CO2 is beneficial because it is not allergenic nor nephrotoxic and has no dose limit due to excretion by the respiratory system. However, CO2 also has risks, such as organ ischemia and emboli. It is also contraindicated for multiple conditions and procedures.

 Gadolinium is another off-label, but well studied alternative to iodinated contrast dyes. Gadolinium is advantageous since it has a low risk of nephrotoxicity. However, it is restricted by the necessity of small dosages and has limited ability to generate high quality angiographic images.

A final broad recommendation is the creation of a centralized hospital command for the allocation and distribution of iodinated contrast dye. Instead of leaving each department to handle the crisis on its own, the creation of a multidisciplinary, multispecialty, and centralized command that can effectively coordinate a hospital-wide response during this critical period is essential. This centralization of command can remove ambiguity and the burden of procurement and allocation from individual physicians and departments. This strategy can allow for more equitable and balanced distributions of limited resources.

In conclusion, although the current ICM shortage is cause for great concern, the future is promising. The Shanghai factory has reopened and other factories across the world have begun to ramp up their ICM supply to help mitigate the crisis.

 A combination of patience, effective triaging, alternative imaging, alternative contrast agents, and novel command structures will enable radiology to weather this storm and fully return to normal in the near future.

1. Reeder SB, Hess CP, Zaharchuk G, Moy L. Editorial for “Magnetic resonance imaging as an alternative to contrast-enhanced computed tomography to mitigate iodinated contrast shortages in the United States: recommendations from the International Society for Magnetic Resonance in medicine. 

 2022 Jun 2. doi: 10.1002/jmri.28282. Online ahead of print.

2. Keefe NA, Desai KR, Kohi MP, Salazar GM. Interventional radiology approach to contrast media preservation strategies. 

 2022 May 19;S1051-0443(22)00940-X. doi: 10:1016/j.jvir.2022.05.011. Online ahead of print.

3. Hicks L. Global contrast media shortage blamed on COVID lockdown in China. Medscape. Available at: 

https://www.medscape.com/viewarticle/973810

 . Published May 11, 2022. Accessed June 21, 2022.

Articles

As the iodinated contrast media shortage continues to have a significant adverse effect on radiology, these authors assess the pros and cons of emerging strategies and imaging alternatives.

Iodinated Contrast Media Shortage: Practical Solutions and Applications in Radiology

Over the past several years, radiology has adapted to new technologies and modalities to enhance both the effectiveness and accessibility of medical education. For example, flipped classroom techniques and educational gaming applications have emerged as creative methods to deliver interactive radiology content. However, social media remains an underutilized space that is filled with potential to serve as a remote learning tool for teaching trainees and medical students.

As an image-based specialty, radiology stands to gain the most from educational trends encouraging quick presentation, processing, and response. In the past two decades, radiology has adopted these platforms for a variety of uses including but not limited to networking with colleagues and students around the world, sharing interesting patient cases, and responding to immediate trends within the field. However, there are several opportunities to expand the role of social media platforms in medical education.

For most of this time, Twitter and Facebook have been the primary social media platforms to engage trainees and medical students online, representing “Social Media 1.0.” In contrast, “Social Media 2.0” reflects a shift in the virtual landscape in which didactic vehicles are sought after to engage viewers in more visually oriented ways. This is particularly the case with platforms such as Instagram and TikTok.

Accordingly, let us take a closer look at this evolution and outline both current and future uses for social media platforms in radiology medical education.

Twitter is one of the most popular social media platforms for professional networking and education in radiology. Online learning through Twitter is continuous and personalized for users to engage in self-improvement, networking, shared cases, and journal clubs. Jaffe and colleagues summarized the primary ways Twitter is and can be used in medical education.

 Educators can share discrete concepts or facts through a basic tweet, or they can link tweets sequentially using images, polling, or reference links to create a lesson. Posing clinical questions or sharing links to case reports and studies can prompt conversation and discussion in real-time.

In another intriguing use case with the University of Chicago Internal Medicine Residency Program, Bergl and colleagues evaluated a chief resident-controlled Twitter account that aimed to advance its program’s educational mission.

 These authors found that 69 percent of 61 residents believed that their overall education was enhanced from tweets related to the teaching points from morning reports, pathology from interesting cases, and educational radiographs/scans.

Twitter can facilitate discussion and engagement between radiologists, residents, and medical students across the country as well. Interestingly, Kauffman and colleagues found that the most engaging radiology content on Twitter are case images and scroll-through videos while news links received the fewest engagement in terms of retweets and likes.

 For radiology, this finding may signal the need to shift our focus toward establishing a larger presence on alternative platforms.

Radiology has a well-established presence on Facebook. Facebook serves both as a marketing and branding tool for radiologists and their practices/organizations. Groups on Facebook, such as Radiology Chicks and Breast Imaging Radiologists, have long been active as a community hub for radiologists to share meaningful cases or discuss broader trends in practice, technology, and education. Similarly, groups related to specific diseases such as breast cancer or patient support groups exist for radiologists to communicate directly with patients and share high-quality information. Similar to Twitter, Facebook groups have also been used to foster learning opportunities between medical students, radiology residents, and practicing physicians. The ability of those in radiology to utilize social media effectively is clear, but Twitter and Facebook only represent the beginning stages of a broader campaign to raise awareness, highlight the field, and innovate medical education.

Instagram, on the other hand, primarily delivers content through images and videos with captions, making it particularly well-suited for radiology. Currently, there are several high-volume accounts, such as @radiopaedia and @thexraydoctor, that promote radiology educational material. Shafer and colleagues demonstrated the potential effectiveness of Instagram as a vehicle for radiology education through their Instagram account, CTisus.

 In under two years, their consistent and diverse catalogue of posts has generated meaningful engagement as the account has accumulated over 6,000 followers, and they have reached an international audience. Notably, the majority of their followers are 25 to 34 years old, which represents the age of the vast majority of medical students and radiology residents.

During the 2020 National Residency Match Program (NRMP) application cycle, Johnson and colleagues found that radiology residency programs were most active on Instagram (58.9 percent) compared to Twitter (29.3 percent) or Facebook (29.55 percent).

 Given this interest and level of engagement, the utilization of image-based platforms to reach medical students interested in radiology, residents, and the general public should be pursued.

While Instagram is primarily suited for image- and video-based delivery, TikTok’s content form is exclusively video. TikTok is the latest addition to the suite of social media platforms and has appeared to gain a large amount of platform users throughout the COVID-19 pandemic. The primary use case on TikTok is not for education, but neither were Twitter or Facebook in their early development. The novelty of TikTok is an opportunity for the field of radiology to find a footing in the social media environment of the 2020s and generate both educational and creative radiology content that can be widely disseminated. 

Similar to Instagram and Twitter, TikTok content is received by “followers” of an account. However, unlike any other social media platform, TikTok users frequently spend time on the app on their “For You” page, a curated, endless series of posts displaying personalized content. Thus, TikTok may allow for radiology content to be shared without limits, increasing interest and engagement with the field.

Diversifying the platforms in which case studies, articles, and other educational material are shared should be encouraged as our understanding and use of novel modalities matures. Ultimately, Social Media 2.0 offers compelling platforms that may serve as supplementary means to promote the field of radiology.

Benefits of Adopting a Novel Social Media Strategy

The opportunity for a stronger radiology presence on social media is clear, and the field is uniquely situated to integrate image-rich platforms into the education of trainees and medical students. As radiology residency programs seek ways to innovate their educational curriculums, emerging platforms can be used to offer students increased flexibility and convenience. Social Media 2.0 can serve as a conduit through which residents and faculty may expose radiology to and engage with medical students.

Active learning and peer-to-peer interaction are key concepts that are integral to social media use in radiology medical education. By “following” radiology accounts that use images and share relevant cases, learners seek out the material that provides the highest value and a means of interacting with fellow students or trainees as well as faculty members. This can ultimately promote collegiality throughout all levels of training.

Importantly, these interactions are not limited to people within an institution or within a specialty as social media can expand opportunities for networking and collaboration. Furthermore, unlike in-person lectures at any institution, these radiology posts and threads remain visible for current and future students and physicians internationally, dissolving geographic boundaries.

Finally, Social Media 2.0 is live and responsive to immediate trends, and image-rich platforms enable innovation in radiology and compelling insights to be shared and discussed in real time. Social Media 2.0 is already in its early stages. With sufficient investment, radiologists can seize this period to increase awareness about the field, enhance collaboration and engagement, and augment medical education for trainees and students more effectively than ever before.

1. Jaffe RC, O'Glasser AY, Brooks M, Chapman M, Breu AC, Wray CM. Your @Attending will #tweet you now: using Twitter in medical education. 

 2020;95(10):1618. doi: 10.1097/ACM.0000000000003314. PMID: 32195691.

2. Bergl PA, Narang A, Arora VM. Maintaining a Twitter feed to advance an internal medicine residency program's educational mission. 

3. Kauffman L, Weisberg EM, Zember WF, Fishman EK. #RadEd: how and why to use Twitter for online radiology education. 

4. Shafer S, Johnson MB, Thomas RB, Johnson PT, Fishman EK. Instagram as a vehicle for education: what radiology educators need to know. 

5. Johnson JL, Bhatia N, West DL, Safdar NM. Leveraging social media and web presence to discuss and promote diversity, equity, and inclusion in radiology. 

The enhanced immediacy, peer-to-peer interaction and networking capabilities of social media platforms, particularly newer vehicles such as Instagram and TikTok, may help reinvent educational models in radiology.

Social Media 2.0: An Emerging Space for Radiology Education

Much of the modern technology used in interventional radiology has been developed by biomedical engineers. For example, in 2018, researchers used bioprinting and microfabrication techniques to develop novel in vitro vascular models to help interventional radiologists study complex vascular procedures.

Biomedical engineers are trained in the principles of physics and mathematical computation for the development of safe and effective medical devices that best fit the needs of medical providers and patients. Medical students, residents, fellows, and attending physicians generally have very little exposure, if any, to these principles during their respective curricula and training.

Conversely, biomedical engineers generally do not interface directly with patients to the same extent as physicians and medical trainees. Therefore, they may not fully understand the specific needs of patients in the same way that medical professionals do. For these reasons, it is important for interventional radiologists and biomedical engineers to collaborate closely to develop medical technology that is optimally designed to meet patient needs and maximize health outcomes.

Many biotechnology companies that specialize in the development of radiological devices were founded through the collaboration of both engineers and physicians. The epitome of this symbiotic relationship is the evolution of Cook Medical, Inc., in the 1960s. This company was founded by William Cook, an entrepreneur, who partnered with Charles Dotter, MD, the father of interventional medicine. They collaborated to create new devices needed by the medical community for minimally invasive procedures, including angioplasty and the earliest interventional radiology techniques.

Renerva is another company that was founded by biomedical engineers for the purpose of helping medical professionals. Renerva developed a product known as peripheral nerve matrix, which is an implantable modality physicians may employ to help improve the outcomes of procedures for treating peripheral nerve injuries.

Due to the variation between peripheral nerve reconstruction techniques among surgical specialties, it was important for physicians to consider with engineers how the product should be used to help ensure maximal recovery for patients.

Interventional radiologists can gain a deeper understanding of how engineers develop new medical technology by consulting in or even leading biotechnology companies. Radiologists can explain and demonstrate to engineers how they use their medical devices in the clinical or hospital setting. Radiologists may also conduct translational and clinical research on bioengineered technology to further understand how to optimize the outcomes and safety of novel technology for specific applications, such as treating specific diseases or training residents and fellows to perform procedures.

To develop better medical devices, it is necessary for biomedical engineers to more fully understand how radiologists utilize technology in practice. Interventionalists can help engineers identify unmet clinical needs that serve as the basis for the generation of new ideas for medical devices. Therefore, engineers can further benefit from observing interventional radiologists in the clinical setting to gain a clearer understanding of how their devices are used in real time and where certain pitfalls or inconveniences can occur during use of each device.

Moreover, it is well established in the literature that 3D printing has been frequently utilized in interventional radiology to help with training and guidance for various procedures. For instance, researchers have developed 3D-printed patient-specific models of temporal bones designed to prepare surgeons for performing middle cranial fossa surgery.

 In addition to its role in pre-procedure planning, 3D printing has also been used in the training of interventionalists and in patient education. 3D printing is a prime example of the application of biomedical engineering to improvement of patient outcomes in interventional radiology. The overall success of 3D printing in interventional radiology thus far shows that the seamless integration of engineering into the practice of radiology is imperative for improved patient care in the future.

The skill sets of biomedical engineers and interventional radiologists are different but overlap in important ways regarding patient care. Interdisciplinary teams consisting of medical professionals from multiple specialties have been vital in the continuity of care for many decades. This concept of multidisciplinary teamwork can easily be applied to the collaboration between engineers and radiologists in creating better medical devices to address the evolving needs of patients and their providers. The bridge between engineering and radiology is important for the overall improvement of outcomes and safety for patients undergoing innovative minimally invasive, image-guided interventions.

1. Li X, Moosavi-Basri SM, Sheth R, Wang X, Zhang YS. Bioengineered in vitro vascular models for applications in interventional radiology. 

https://www.drugwatch.com/manufacturers/cook-medical/

3. Yeomans M. Pitt startup hits a nerve for new CEO. University of Pittsburgh Innovation Institute. Available at: 

https://www.innovation.pitt.edu/2017/11/renerva/

 . Published November 22, 2017. Accessed December 30, 2021.

4. Freiser ME, Ghodadra A, Hirsch BE, McCall AA. Evaluation of 3D printed temporal bone models in preparation for middle cranial fossa surgery. 

5. Freiser ME, Ghodadra A, McCall AA, Shaffer AD, Magnetta M, Jabbour N. Operable, low-cost, high-resolution, patient-specific 3D printed temporal bones for surgical simulation and evaluation. 

Multidisciplinary collaboration between innovators in two seemingly disparate fields have led to significant advances.

Pathways to Medical Device Innovation: Exploring Collaboration Between Interventional Radiologists and Biomedical Engineers

The prompt and accurate results of an imaging study can be the difference between life and death. Yet the number of practicing radiologists in the United States is likely insufficient to meet the growing demand. This shortage is also projected to worsen, and according to the Association of American Medical Colleges (AAMC), the U.S. is projected to have a shortage of 17,000 to 42,000 radiologists, pathologists, and psychiatrists by 2033.

 On average, the number of imaging studies increases by a rate of up to five percent per year, but the number of radiology residency positions only increases by two percent.

This shortage has a dramatic impact on patient care. A shortage of radiologists leads to increased turnaround times for study results to be generated, which can negatively impact patient outcomes. One recent study found that radiology imaging delays are an independent predictor of length of hospital stay.

 Another recent study found it took more than three hours to generate a report from an average CT study with the radiologist being the bottleneck 42 percent of the time.

 This delay in clinically pertinent information can have a significant impact on patients. These delays needlessly burden health systems, patients, and insurers, and could be resolved by improved imaging coverage. Although the situation might appear dire, there are many potential solutions.

The first and most immediate solution would be an increase in the number of radiology residency positions.

 The number of positions is largely determined by Medicare, and there have only been marginal increases over the years in radiology. In 2006, there were 1,011 radiology residency positions. In 2020, there were 1,113 radiology residency positions. However, this slow increase has begun to change as Congress passed a graduate medical education (GME) expansion in 2020, which added 1,000 new residency spots, many of which are likely to be radiology positions.

Increasing medical student awareness of the specialty is another promising way to combat the shortage.

 Medical students often have little exposure to the radiology specialty, and a recent study found that only 35 percent had completed a radiology rotation by graduation.

 This could be remedied by promoting radiology as a core rotation in medical school as well as increasing the amount of radiology material that is covered during the preclinical curriculum. One study found that adding just 2.5 hours of radiology lectures to the first year of medical school significantly increased student interest in radiology, and increased the likelihood of students completing a radiology rotation later in the curriculum.

 This is a promising solution since more medical students interested in and matching into radiology could potentially reduce the impact of the radiologist shortage.

Another solution to this workforce challenge is achieving improvements in radiologist efficiency.

 Many studies have investigated potential methods by which radiologists can increase efficiency. Promising solutions include decreasing distraction and integrating the utilization of artificial intelligence (AI) in practice.

 Interruptions due to phone calls, emails, and consent forms can hinder a radiologist’s workflow, potentially leading to decreased performance and less informed consultations.

Reductions of these distractions through the use of reading room coordinators and enhanced communication workflows are often pursued as solutions for improving efficiency. Additionally, AI enables radiologists to perform their roles with greater efficiency. Although unlikely to replace the role of the radiologist, AI can be used to help with measuring lesions, comparing studies, and triaging scans that are at an increased risk of being urgent. One study found that AI could be used to select which chest X-rays were more likely to be abnormal, and then prioritized those for interpretation by radiologists.

 This method was able to decrease the average delay in interpretation of abnormal scans from 11.2 days to 2.7 days.

Although current trends in the number of practicing radiologists may seem concerning, the future is bright. There are many effective solutions to this problem, all of which are simultaneously being pursued. Many medical schools are integrating more radiology material into the curriculum, radiology residency positions are being expanded, and radiologists are becoming more efficient each year. These trends are promising for the future of the field and with sufficient action, the shortage can be addressed and possibly reversed.

1. Dall T, Reynolds D, Chakabarti R, et al. The complexities of physician supply and demand: projections from 2018 to 2033. Washington, D.C. Associaion of American Medical Colleges. Available at: 

https://www.aamc.org/system/files/2020-06/stratcomm-aamc-physician-workforce-projections-june-2020.pdf

 . Published June 2020. Accessed January 20, 2022.

2. Smith-Bindman R, Kwan ML, Marlow EC, et al. Trends in use of medical imaging in US healthcare systems and in Ontario, Canada, 2000-2016. 

3. Courane S, Conway R, Creagh D, et al. Radiology imaging delays as independent predictors of length of hospital stays for emergency medical admissions. 

4. Perotte R, Lewin G, Tambe U, et al. Improving emergency department flow: reducing turnaround time for emergent CT scans. 

 2018 Dec 5;2018:897-906. eCollection 2018.

5. Prezzia C, Vorona G, Greenspan R, et al. Fourth-year medical student opinions and basic knowledge regarding the field of radiology. 

6. Branstetter B, Humphrey A, Schumann J. The long-term impact of preclinical education on medical students’ opinions about radiology. 

7. Dargan R. Artificial intelligence boost efficiency and quality in radiology practice. Radiological Society of North America (RSNA). Available at: 

https://www.rsna.org/news/2019/march/artificial-intelligence-boosts-efficiency

 . Published March 18, 2019. Accessed January 20, 2022.

8. Lee MH, Schemmel AJ, Pooler BD. Radiology workflow dynamics: how workflow patterns impact radiologist perceptions of workplace satisfaction. 

While current projections suggest a shortage of radiologists in the future, promising developments with radiology residency positions, medical student awareness of the field and AI-aided efficiencies could be game changers. 

Are We Prepared for a Looming Radiologist Shortage?

COVID-19 is here to stay, at least for now, and so are many changes brought on by the need for adaptability during the early days of the pandemic. The necessity for physical separation drove many employers in all sectors, including medicine, to embrace remote work en masse in a way that had previously not been common, nor accepted in the mainstream. Old stereotypes of working from home have shifted from a luxury to something that is reasonable for anyone to seek out as their primary employment location. 

Remote working has seen a huge increase from pre-pandemic levels. 

of all workers will still be working remotely by the end of this

 Extrapolation of this data suggest that 36.2 million of the American workforce will be working from home by 2025, almost double the incidence before the advent of the pandemic. 

Advances in technology have made remote work equally, if not more, efficient than traditional office work. Many of the lessons learned from the private sector can be applied to the medical field. Although the adoption of telemedicine has been slow in the past, it is now more viable than ever with a corresponding boom in teleradiology.

With regard to our specialty, teleradiology has frequently been used to offset the exploding imaging requirement during off-service hours or otherwise allow for fulfillment of diagnostic responsibilities at off-site locations. 

off-hours teleradiology has jumped from 15

 With emergency department imaging use continuing to rise and new techniques further increasing the imaging volume expectations, a symbiotic relationship and understanding of the value of teleradiology is of great importance, even to those who are not interested in remote work.

The value of remote work exists not only in individual preference, but in more concrete benefits to the radiologist as well as the patient and hospital. For those who enjoy working from home, being allowed to perform some responsibilities remotely appears to confer resistance to the ever -present threat of physician burnout. A survey of radiation oncologists during the height of the original wave of the pandemic demonstrated a surprising reduction in burnout from 40 percent the previous year to 32 percent in May 2020.

 They attributed this resilience to their employees’ attitudes regarding working from home with 74 percent reporting a positive experience. Additionally, despite previous misconceptions, working from a home environment outside of a traditional office work setting appears to confer an increased – not decreased – productivity. Remote workers reported increased focus and less unproductive time.

 There are also the benefits of reduced commute time and cost, and the additional free time that comes with that. 

Diagnostic reading work, in particular, is amenable to remote productivity compared to most other telemedicine work since no physical proximity between physician and patient or other staff is necessary. Since remote work can theoretically be done at any distance, these radiologists can efficiently cover large networks of low-volume rural hospitals without any commute.

Likewise, the use of remote radiologists either in-house or externally sourced to cover overnight call shifts allows physicians to still work during normal hours and reduces the often burnout-inducing frustration of call shifts.

This is not to say that remote work is without its flaws. A common complaint for those who mostly work from home is the inability to disassociate work from home life. It is important to quarantine work responsibilities in a home office, and the lack of one may inhibit the draw of effective remote work. 

Radiology, in particular, requires a high-quality and expensive workstation to simulate the reading experience of in-house work and guarantee the same end product. While many institutions may supply this equipment, this is not universal. Also, remote physicians working across state lines are required to be licensed in both states, reducing a radiologist’s ability to easily do work in multiple states although the COVID-19 pandemic led to temporary reprieve of some of these regulations.

 These regulations may serve to protect radiologists from international outsourcing though. 

Lastly, the complexities of remote work may also be a hinderance to those who are not technologically inclined and may confer challenges in technical support for off-site hardware.

Whether done as a small component of a traditional radiology position or via a stand-alone position, teleradiology has an important role to play in modern medicine. Teleradiologists can help offset burnout and improve productivity and bring increased coverage to rural areas that may not be able to have additional full-time staff. Many radiology responsibilities can be done at home with the increased availability of remote collaboration software. Hospitals should work to offer additional opportunities for staff to spend days without in-person needs at home workstations. In this new, post-COVID landscape, remote work is more accepted, viable, and valuable than ever. It would be a mistake for radiology not to embrace these changes.

1. Ioannou L. 1 in 4 Americans will be working remotely in 2021, Upwork survey reveals. CNBC. Published February 6, 2021. Accessed December 14, 2021. 

2. Hanna TN, Steenburg SD, Rosenkrantz AB, Pyatt RS Jr, Duszak R Jr, Friedberg EB. Emerging challenges and opportunities in the evolution of teleradiology. 

3. Hoffman KE, Garner D, Koong AC, Woodward WA. Understanding the intersection of working from home and burnout to optimize post-COVID19 work arrangements in radiation oncology. 

 2020;108(2):370-373. doi:10.1016/j.ijrobp.2020.06.062

4. Airtasker. The benefits of working from home. Airtasker Blog. Published March 31, 2020. Accessed December 14, 2021. 

5. Van Moore A, Allen B, Campbell SC, et al. Teleradiology: American College of Radiology. American College of Radiology. 

https://www.acr.org/Practice-Management-Quality-Informatics/Legal-Practices/Teleradiology

With reports of increased productivity and reduced burnout, teleradiology may rapidly become the new normal. 

Exploring the Opportunities of Teleradiology in the Wake of COVID-19

Virtual biopsy may provide a robust, non-invasive alternative in the surveillance and management of several types of cancer. This new imaging-based technique can extract encoded data from routine medical imaging scans and formulate likelihoods to help characterize tissue for the purposes of screening for cancer, diagnosing and grading cancer, planning oncologic treatment, and predicting prognosis of disease--all without any surgical or invasive intervention.

Although its use has been primarily studied in the oncologic setting, it can potentially be used for any disease process that requires analysis of its pathogenesis. Here, we discuss the technique of virtual biopsy, the variety of ways physicians can utilize it, and its impact on the outcomes of patients and healthcare.

Virtual biopsy is a non-invasive technique to characterize tissue found in imaging studies. A great wealth of information can be interpreted by radiologists on imaging scans. However, additional encrypted data regarding the tissue’s intrinsic features, gene expression patterns, gene mutations, and molecular pathophysiology are still invisible to the human eye.

Access to this additional information can be granted through the use of radiomics. Radiomics is the applied field of radiogenomics which focuses on extracting objective, quantitative data found in images

. Generally, the workflow includes obtaining the image, processing the image, creating a volume of interest, and then extracting mathematical data in that volume

. This can be possible through several imaging modalities, such as CT, MRI, PET, radiographs, and ultrasound imaging

. Examples of data collected include volume, shape, density, and location in addition to complex mathematical metrics assessing textures and dimensional analysis

Through radiogenomics, these phenotypic data can then be correlated with previous genetic data and can reveal and provide insight to the molecular pathophysiology of disease by mapping out the gene expression of the tissue with the assistance of artificial intelligence and characterization algorithms

Virtual biopsy offers an alternative to traditional surgical biopsies which are used to obtain histological data for the same purpose of diagnosis and treatment planning. Compared to traditional biopsy, the benefits are numerous. With virtual biopsy being a non-invasive procedure, there is a lesser risk of complications to the patient

. Additionally, there is a lower cost associated with the service compared to traditional biopsies due to eliminating the operating room

. Further, the patient would benefit from a quicker report on their tumor pathology, affecting their treatment timetable

. Lastly, virtual biopsies can assist in making surgical biopsies even more conclusive, as discussed next.

One area where virtual biopsy can enhance clinical outcomes is in accurate, early cancer detection. When patients undergo low-specificity screening, it generates increased risk for patients in the form of unnecessary further imaging studies and invasive biopsies of suspected lesions which could be benign. This further workup creates increased radiation and surgical risk exposure, in addition to the increased costs of these services

One example of this narrative is in the setting of lung nodules identified on low-dose CT screening. In a study conducted by Ma. et al., researchers obtained 127 indeterminate pulmonary nodules that posed the question of malignancy

. They were able to identify 583 texture-based features, such as nodule intensity and tumor heterogeneity. After formulating a model, the researchers were able to predict malignancy of the nodules correctly 82.7 percent of the time

Even more remarkable, in another study conducted by Yang et al., virtual biopsy was able to correctly identify malignancies in the setting of complex ground-glass opacities, as well. Their work found that the volume and diameter of ground glass opacity tumors showed correlation with the EGFR status of the tumors, also shedding light on the potential treatment options for the patient

Another area where virtual biopsy can improve cancer screening is in the setting of pancreatic neoplasms. Although there is no routine screening for pancreatic cancer, certain patient populations that are high-risk may undergo routine ultrasound or MR imaging screening

. High-risk patients typically have a family history, symptomatic pancreatitis, new-onset diabetes, or asymptomatic mucinous cystic lesions found incidentally

. These patients can be subject to risky surgical intervention if their pancreatic lesion seems suspicious based on qualitative features on imaging.

However, in one study conducted by Permuth et al., researchers were able to identify 14 radiomic features (11 textural and three non-textural) that differentiated malignant pancreatic neoplasms from benign intraductal papillary mucinous neoplasms. The prediction model that incorporated the 14 radiomic features collectively proved to be fairly accurate in their diagnosis (AUC=0.77 and P<0.05). In fact, the study also reported that three of the cases that had worrisome features on pre-operative scanning were correctly identified as true negatives by radiomic analysis, displaying higher accuracy than conventional feature analysis

. This, in turn, could save patients from particularly invasive biopsies in the future if further studies can reproduce and validate the models used in this study.

Use of Virtual Biopsy in Diagnosing Tumors

There are several applications where virtual biopsies can help diagnose malignant processes in the body. One example of this is in the setting of head and neck squamous cell carcinoma. In a study conducted by Ren et al., using MR imaging, researchers were able to formulate a predictive model that stratified whether the head and neck cancer was high-grade or low-grade in pathology.

Using a total of 970 radiomic features extracted from T2-weighted and contrast enhanced T1-weighted MR images, the study was able to discriminate WHO class grade I-II tumors from grades III-IV head and neck squamous carcinoma within the images

. The final testing cohort yielded an AUC of 0.853 and 0.849 for high grade and low grade respectively, proving it to be fairly accurate

Similarly, MR imaging can also be used for grading neurological tumors. Another study conducted by Bai et al., utilized radiomic data, such as the water molecular diffusion heterogeneity index (WMDHI) and the mean kurtosis values for predicting the grade of gliomas. The study concluded that both of these metrics were higher in high-grade gliomas when compared to low-grade gliomas (P<.05). With the same metrics, the researchers determined specific cut-off values for differentiating high-grade gliomas from low-grade gliomas. After cross-referencing with subsequent surgical biopsies, the sensitivity of 

 the metrics was 92.9 percent, with specificity being 100 percent, demonstrating itself as a precise model

Another paradigm where virtual biopsy can aid in the diagnosis of malignancy is in the setting of invasive ductal carcinoma. In a study conducted by Guo et al., researchers were able to identify 25 computerized texture analysis features (such as neighborhood gray-tone difference matrix-based features and their wavelet decomposition) when describing echogenicity patterns of breast lesions.

The texture analysis of these features yielded a “busyness” score, where the average value for estrogen receptor positive (ER+), progesterone receptor positive (PR+) and human epidermal growth factor receptor 2 (HER2-) tumors was 1.402 and in ER- PR- and HER2- tumors was 1.912 (P<0.001). This study shows there is potential for a reliable model to accurately identify the molecular subtype of breast cancer, not only aiding in diagnosis but also influencing treatment options

Use of Virtual Biopsy in Treatment Planning

Virtual biopsy can not only aid in diagnosis of tumors, but it can also use radiogenomic data to go a step further to help plan the treatments, as well. For example, one study examined its application in treatment planning for patients with glioblastoma. Previous research established that the isocitrate dehydrogenase mutation in glioblastoma is associated with a slower progression rate.

Patients affected with glioblastoma tumors that carry this mutation have completely different treatment options in terms of urgency of surgical intervention and adjuvant therapy. In a study conducted by Arnout et al., through MR imaging and radiogenomics, his team was able to correctly identify IDH status in three different cohorts at an 87 percent-to-89 percent accuracy when confirmed by subsequent brain biopsies

Virtual biopsies can further provide insight on how to perform accurate surgical biopsies for treatment planning. Tumors that are “high grade” tend to exhibit the highest amount of tumor heterogeneity, which alludes to the differential genetic expression across the same tumor mass. This becomes important clinically because the sample obtained during biopsy may or may not paint the whole picture regarding the genetic makeup of the tumor--ultimately impacting how effective the treatment of choice will be.

However, with virtual biopsy, three-dimensional images of the patient’s tumor can be obtained via CT scanning. Using radiomics combined with radiogenomic data, this will allow the physician to map out the areas with the most genetic heterogeneity of the tumor, revealing the most ideal location to biopsy the mass and allowing for a conclusive and accurate biopsy

Virtual biopsy further proves to deliver comprehensive cancer care for patients by providing data on the prognosis for patients, as studied in several of the following tumor settings. One context where virtual biopsies provide prognostic data is bladder cancer. A study conducted by Lin et al., looked to find a predictive model for the prognosis of transitional cell carcinoma of the bladder. The study was able to identify seven radiomic features (wavelets and gradient orientations), which were then used to build a radiomics predictive model. Using the model, the researchers were able to stratify the patients into high-risk or low-risk groups in regard to progression-free tumor survival

Further work conducted by Iwatate et al., looked at the prevalence of p53 gene mutations in the setting of pancreatic ductal adenocarcinoma. The study iterated that the expression of the p53 gene mutation in the pancreatic malignancy was a significant factor for a poorer prognosis. With this, the researchers set out to develop a model that was able to predict if the pancreatic lesion exhibited the p53 mutation based on quantitative imaging features and radiogenomics

Lastly, a study conducted by Tokuda et al., sought to find a predictive model for the prognosis of breast cancer patients regarding recurrence of their disease. This study utilized a previously validated risk-stratifying tool to characterize the breast tumors as high-risk or low-risk for tumor recurrence based on their genetic mutations. Then, using MR imaging and radiomics, researchers concluded that factors, such as medium kinetic volume ratio and delayed phase kurtosis were associated with higher tumor recurrence. This allowed for the stratification of patients into high and low risk of reoccurrence groups

Virtual biopsy has shown to be effective in a variety of manners, including increasing the accuracy of cancer screening, helping diagnose and grade various tumors, and providing input in the treatment and prognosis of patients afflicted by oncologic disease. By virtue of being a non-invasive technique, elimination of unnecessary surgical risk and associated complications will contribute to decreased morbidity and mortality. Additionally, through its increased precision in cancer screening, patients will benefit from earlier diagnosis, directly improving their prognosis in some cases.

Further, patients will also receive tailored treatments consistent with their cancer’s mutational status and prognosis. Lastly, the healthcare system can expect to see a decreased need for invasive procedures, such as costly surgical biopsies, in turn reducing the economic burden cancer creates.

However, being a newer technology, there are some limitations, as well. Due to large amounts of data, there are increased computing power and storage requirements that not all institutions have the capacity to accommodate

. Next, the statistical approaches involved to analyze the data need to be fine-tuned: validating these models across several imaging platforms and patient populations with varying genetic makeups is a barrier

. Lastly, the lack of standardization of acquisition parameters used to derive predictive models and inconsistent radiomic methods further hinder the reproducibility of virtual biopsy

This being said, the potential is vast for virtual biopsies, radiomics, and radiogenomics. Medicine is moving in the direction of non-invasive procedures and virtual biopsy fits the trend. Patients can benefit from procedures that can be performed in the outpatient setting, while still benefiting from robust data about their disease that will help their physician treat them with arguably similar accuracy compared to their surgical counterparts.

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6. L. Gillies, R. J., & Schabath, M. B. (2020). Radiomics improves cancer screening and early detection. Cancer Epidemiology and Prevention Biomarkers, 29(12), 2556-2567.

7. Permuth, J. B., Choi, J., Balarunathan, Y., Kim, J., Chen, D. T., Chen, L., ... & Malafa, M. (2016). Combining radiomic features with a miRNA classifier may improve prediction of malignant pathology for pancreatic intraductal papillary mucinous neoplasms. Oncotarget, 7(52), 85785.

8. M. Ren J, Tian J, Yuan Y, Dong D, Li X, Shi Y, Tao X. Magnetic resonance imaging based radiomics signature for the preoperative discrimination of stage I-II and III-IV head and neck squamous cell carcinoma. Eur J Radiol. 2018 Sep;106:1-6. doi: 10.1016/j.ejrad.2018.07.002. Epub 2018 Jul 4. PMID: 30150029.

9. O. Bai, Y., Lin, Y., Tian, J., Shi, D., Cheng, J., Haacke, E. M., ... & Wang, M. (2016). Grading of gliomas by using monoexponential, biexponential, and stretched exponential diffusion-weighted MR imaging and diffusion kurtosis MR imaging. Radiology, 278(2), 496-504.

10. N. Guo, Y., Hu, Y., Qiao, M., Wang, Y., Yu, J., Li, J., & Chang, C. (2018). Radiomics analysis on ultrasound for prediction of biologic behavior in breast invasive ductal carcinoma. Clinical breast cancer, 18(3), e335-e344.

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8. Iwatate, Y., Hoshino, I., Yokota, H. et al. Radiogenomics for predicting p53 status, PD-L1 expression, and prognosis with machine learning in pancreatic cancer. Br J Cancer 123, 1253–1261 (2020). 

https://doi.org/10.1038/s41416-020-0997-1

12. Martin-Gonzalez, P., Crispin-Ortuzar, M., Rundo, L., Delgado-Ortet, M., Reinius, M., Beer, L., ... & Sala, E. (2020). Integrative radiogenomics for virtual biopsy and treatment monitoring in ovarian cancer. Insights into Imaging, 11(1), 1-10.

13. Lin P, Wen DY, Chen L, Li X, Li SH, Yan HB, He RQ, Chen G, He Y, Yang H. A radiogenomics signature for predicting the clinical outcome of bladder urothelial carcinoma. Eur Radiol. 2020 Jan;30(1):547-557. doi: 10.1007/s00330-019-06371-w. Epub 2019 Aug 8. PMID: 31396730.

14. Iwatate, Y., Hoshino, I., Yokota, H. et al. Radiogenomics for predicting p53 status, PD-L1 expression, and prognosis with machine learning in pancreatic cancer. Br J Cancer 123, 1253 1261 (2020). 

15 (10. Tokuda, Y., Yanagawa, M., Minamitani, K., Naoi, Y., Noguchi, S., & Tomiyama, N. (2020). Radiogenomics of magnetic resonance imaging and a new multi-gene classifier for predicting recurrence prognosis in estrogen receptor-positive breast cancer: A preliminary study. Medicine, 99(16).

16. Lohmann, P., Bousabarah, K., Hoevels, M. 

 Radiomics in radiation oncology—basics, methods, and limitations. 

The potential opportunities are numerous for virtual biopsies, radiomics, and radiogenomics.

Virtual Biopsy: A Safer Future for Cancer Management 

Due to advancements in catheter-based therapies in interventional radiology, conditions that once required large open surgeries, months of recovery, and had many associated complications, are now being treated with minimally invasive procedures by radiologists. One such intervention is uterine fibroid embolization (UFE). Although UFE has been performed for almost 25 years, the procedure continues to evolve.

Uterine fibroids are the most common benign tumor of reproductive age women, and they can cause debilitating symptoms. In many instances, conservative medical management fails or is associated with an unfavorable side effect profile. In these cases, the gold standard has been either myomectomy or hysterectomy. However, both are major invasive surgeries, associated with significant costs, long hospitalizations/recovery, and significant morbidity. Given recent concerns regarding long-term effects on cardiovascular and hormonal health, uterine sparing therapies have grown in popularity.

The need for a growing role for interventional radiologists.

Mina S. Makary, MD

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