CME Radiology Grand Rounds

This presentation will provide an overview of current techniques and applications for cardiovascular MRI. Accelerated cine imaging techniques will be discussed including compressed sensing and increased acceleration parallel imaging. Regional functional imaging with tissue phase mapping and DENSE will be reviewed. Some new approaches to tissue characterization with T1, T2 and extracellular volume measurements will be presented, along with clinical examples. Finally, newer vascular imaging approaches in the thorax will be outlined including 4D flow and non contrast MRA.

The traditional issue with pediatric CT and radiation is “the balance” between image quality and radiation dose (and risk). While this is a challenging issue to address in and of itself, especially with uncertainties in risk and difficulties with defining quality, there are other important balances which influence the practice of CT that must be considered and are arguably less familiar but more influential than the traditional dose-quality balance. Elements of these other balances include available resources (imaging technology and expertise), varying clinical landscapes, parental expectations, comprehensive and comprehensible information, evidential vs anecdotal decision making, rewards (e.g. performance metrics), and self-referral (including our reports). These apply beyond CT to much of imaging care and material and discussion of the above will emphasize the responsibility of the radiology community in consensus strategies for imaging accountability.

Techniques of biomedical imaging are an integral part of both drug discovery and clinical drug development. High resolution MRI, CT, and ultrasound as well as optically based imaging are established technologies within the pharmaceutical industries’ armamentarium and a core facility for the experimental researcher. Further, functional and molecular imaging promised to streamline the clinical drug development process by providing evident of biological activity of investigational drugs during the initial stages of clinical testing and to inform decision making prior to embarking upon pivotal trials. In this way, it is believed that radiological imaging can influence drug development in the era of personalized medicine. But, for this approach to be valid, it must hold that the imaging biomarker can assess some aspects of the biological activity of the investigational agent that is likely to confer clinical benefit. As yet, few imaging endpoints have been truly establish as surrogates for clinical endpoints, thus the full impact of radiological imaging for the drug developer remains to be realize.

Ultrasound imaging is a widely available, relatively inexpensive, and real-time imaging modality that does not expose patients to radiation and which is the first-line imaging modality for assessment of many organs. Through the introduction of ultrasound contrast agents, the sensitivity and specificity of ultrasound for detection and characterization of focal lesions has been substantially improved. Recently, targeted contrast-enhanced ultrasound imaging (ultrasound molecular imaging) has gained great momentum in preclinical research by the introduction of ultrasound contrast agents that are targeted at molecular markers over-expressed on the vasculature of certain diseases. By combining the advantages of ultrasound with the ability to image molecular signatures of diseases, ultrasound molecular imaging has great potential as a highly sensitive and quantitative method that could be used for various clinical applications, including screening for early stage disease (such as cancer), characterization of focal lesions, quantitative monitoring of disease processes at the molecular level, assisting in image-guided procedures, and confirming target expression for treatment planning and monitoring. In this talk, the concepts of ultrasound molecular imaging are reviewed along with a discussion on current applications in preclinical and clinical research.

The brain is a highly perfused organ, receiving approximately 20% of the cardiac output. Alterations in cerebral blood flow (CBF) occur in cerebrovascular disorders, but regional CBF is also tightly coupled to regional brain function. Accordingly, CBF can be used as a versatile biomarker of regional brain function at rest, in response to sensorimotor or cognitive tasks, in disease states, or to assess the effects of pharmacological therapies and other interventions. A variety of methods exist for monitoring of CBF in vivo, including noninvasive methods based on magnetic resonance and optical signals. This presentation will review the measurement of CBF, with a focus on arterial spin labeled perfusion MRI, and illustrate its applications in basic and clinical neuroscience.

Recent discovery of molecular changes associated with cancers has allowed for application of Molecular Imaging and Targeted Radiotherapy in Oncology using radioactive probes. In this lecture, we will introduce the concept of a theranostic radiopharmaceutical, ie a drug that has both diagnostic and therapeutic properties. For example, the simple formulation sodium iodide has been applied in thyroid cancer as a diagnostic, in the form of 124I-NaI, and as a therapeutic as 131I-NaI. We will discuss how MEK inhibitor therapy effectiveness may be monitored in thyroid cancer using 124I-NaI and PET imaging to show increased uptake and retention sufficient for therapy, and then how 131I-NaI, may be used to induce responses, in the same patient. Another area of rapid advance has been in the development of biologicals as theranostics for therapy in oncology. We will discuss how the specificity of antibodies for a tumor associate antigens, may be used both as a diagnostic to improve staging and patient selection, and for study of transport of toxin and drug immunoconjugates into tumors. The example given with be Zr89 and In111/Lu177 J591 anti-PSMA antibody in prostate cancer. Finally, pediatric oncology applications of the theranostic pair 124I/131I-3F8 anti-GD2 antigen have led to long term responses in CNS recurrences of Neuroblastoma. Theranostic applications in nuclear oncology are being used to select appropriate patients and provide useful therapy for some human neoplasms.

The market is demanding transparency. But that’s not the only reason we are working to bare it all. Transparency in health care creates an informed and engaged consumer, and informed and engaged health care providers. Informed patients and providers are necessary pieces of the puzzle in health care transformation. Of late, we are seeing the good news that we are bending the cost curve. Reports show that Medicare costs have slowed significantly below the growth of the economy—a pace we expect to see continue through 2017. This, though, is only the beginning. Transparency in costs, physician reviews, outcomes, quality measures, and resource allocation to name a few, are a necessary road for us to travel down as we reach for our ultimate goal: value in health care.

Classification systems for aortic dissection provide important guides to clinical decision-making, but the relevance of traditional categorization schemes is being questioned in an era when endovascular techniques are assuming a growing role in the management of this frequently complex and catastrophic event. In recognition of the expanding range of interventional therapies now used as alternatives to conventional treatment approaches, the Working Group on Aortic Diseases of the DEFINE Project developed a categorization system that features the specific anatomic and clinical manifestations of the disease process that are most relevant to contemporary decision-making.

The DISSECT classification system is a mnemonic-based approach to the evaluation of aortic dissection. It guides clinicians through an assessment of 6 critical characteristics that facilitate optimal communication of the most salient details that currently influence the selection of a therapeutic option, including those findings that are key when considering an endovascular procedure, but are not taken into account by the DeBakey or Stanford categorization schemes. The 6 features of aortic dissection include: Duration of disease; Intimal tear location; Size of the dissected aorta; Segmental Extent of aortic involvement; Complications of the dissection, and Thrombus within the aortic false lumen.

In current clinical practice, endovascular therapy is increasingly considered as an alternative to medical management or open surgical repair of aortic dissection. The use of a new system for categorization of aortic dissection, DISSECT, addresses the shortcomings of well-known established schemes devised over 40 years ago before the introduction of endovascular techniques. It will serve as a guide to support a critical analysis of contemporary therapeutic options and inform management decisions based on specific features of the disease pro Stanford type A aortic dissection is the most common form of thoracic aortic dissection, accounting for approximately 60% of all cases. Untreated, this condition has a high mortality, which emphasizes the need for emergency repair. Classic therapy is direct surgical replacement of the ascending aorta with a prosthetic graft and maybe combined aortic valve replacement, reconstruction of the aortic arch and its branches, or both, as clinically indicated. Morbidity and mortality for direct surgical repair both have improved substantially in recent years . Unfortunately, the International Registry of Acute Aortic Dissection showed that approximately 28% of patients with acute type A aortic dissections were considered unfit for open surgery and received only medical management. Survival of these medically managed patients is compromised significantly in both acute and chronic circumstances compared with those who receive direct surgical repair.

Recent improvements in endograft technology raised the consideration that these new shorter, larger-diameter endografts may be useful as a novel endovascular treatment for patients with acute ascending aortic dissection who were considered poor candidates for direct surgical repair. Zimpfer et al. conducted an ex vivo study demonstrating that stentgraft placement for ascending aortic dissection was feasible and could achieve complete exclusion of the false lumen. Isolated case reports describing endovascular repair of ascending aortic dissection have been published, but patient follow-up was extremely limited. Some of these reports identified major complications, including procedural-related cerebral ischemia and progressive aortic valvular insufficiency, and therefore raised serious questions regarding the value of endovascular repair of ascending aortic dissection. On the basis of our previous experience with endovascular repair of aortic dissections, we combined newly designed stent grafts with our endovascular techniques for managing aortic dissection to offer treatment to a select group of patients with ascending aortic dissection.

This presentation will focus on the important role radiologists play in serving as a patient advocate and providing patient centered care. All too often the focus and discussions about advocacy and patient centered care target the physicians and nurses responsible for the treatment of cancer patients. This presentation will provide attendees insight into understanding the profound role that radiologists play as patient advocates and the delivery of patient centered care. Through case studies and other examples, including a video, the speaker will discuss how radiologists directly impact cancer patients psychological well being, coping skills and even their hope for their future which includes the hope patients with metastatic breast cancer have.

Positron emission tomography (PET) and magnetic resonance imaging (MRI) provide complementary data that are routinely analyzed concurrently in research and clinical applications. Simultaneous PET/MRI data acquisition allows the spatial and temporal correlation of the measured signals, creating opportunities impossible to realize using stand-alone instruments. This presentation will briefly review some of the approaches proposed for overcoming the technical challenges in integrating these imaging modalities; discuss the methodological challenges (MR-based attenuation correction) and opportunities (e.g. MR-assisted motion and partial volume effects correction, image-based radiotracer arterial input function estimation); present promising clinical and research applications that highlight the tremendous potential of this novel imaging modality for studying the brain in new ways.

Positron Emission Tomography (PET) has evolved from a clinical research tool to a standard imaging technique with the advent of PET/CT (computed tomography) for diagnosis, staging, and monitoring of response in cancer patients. This presentation will briefly review the evolution of the technology to improve patient care as it is incorporated into the rapidly evolving multi-disciplinary care teams. An overview of the solutions to various challenges of evolving technology, accreditation, and adaptation to multi-modality treatment techniques to allow timely, accurate reporting of these important imaging studies. Future directions to improve this molecular imaging technique using tracers beyond FDG will be discussed including the use of radioisotope based therapies for cancer.

While millions of patients are treated successfully with orthopaedic implants such as spinal fixations and joint replacements, as many as a quarter of patients will experience subsequent complications. MRI is ideal for assessment of soft tissue, but fails near metals due to severe image artifacts. This presentation will review the mechanisms of signal loss, pile-up and distortion artifacts and offer various existing and novel approaches to improve images. These approaches have shown promise in a clinical setting for diagnosis of complications such as spinal cord impingement, osteolysis, wear-induced synovitis and recurrent osteosarcoma.

Lung cancer is the leading cause of cancer related death in the United States, with more than 200,000 newly diagnosed cases each year. Currently the 5-year lung cancer survival probability is approximately 15%; however, tumors detected at smaller sizes are associated with higher survival rates implying that early detection of lung cancer is critical in reducing lung cancer mortality. In 2010, the National Lung Screening Trial (NLST) demonstrated that low-dose CT (LDCT) versus chest radiographic screening reduced lung cancer mortality by 20%. Recently, the United States Preventive Services Task Force (USPSTF) updated their national lung cancer screening guidelines, recommending that an individual aged 55 to 80 years with at least 30 pack-years of smoking and less than 15 years since quitting be screened annually by LDCT. Their decision to extend the screening stopping age to 80 years has initiated debate on the appropriate stopping age. The USPSTF decision was made based on evidence from clinical trials, including NLST, as well as analyses provided by Cancer Intervention and Surveillance Modeling Network (CISNET) consortium. CISNET is an NCI sponsored consortium that uses a comparative statistical modeling approach to estimate the population-level impact of cancer prevention, screening and treatment strategies. On behalf of the CISNET lung group, I will present the CISNET modeling work that was used by the USPSTF during their deliberations on the lung cancer screening recommendations. I will conclude my talk with the implications of advances in genomic medicine on future cancer screening guidelines.

Over the past several decades increasingly, concerns have been raised as to the validity and ability to generalize from published scientific articles. The causes of this problem appears to be multifactorial but include ethical issues, including conflict of interest and redundant publication, and issues relating to the quality of the science and the tendency to over-interpret or “spin” the findings that are being reported.

The rate of retraction of scientific manuscripts has grown ten-fold in the past decade. Nearly half of the retractions, unfortunately, are due to some form of misconduct, including plagiarism, redundant publication, and data falsification. There is ample evidence that conflict of interest particularly as it relates to industry sponsored research also contributes to the problem. Despite recent efforts in mandating trial registration before the study begins, and in making the primary data available for review, these commercially driven problems appear to persist.

Scientifically, the validity of a result is largely dependent on the statistical power of the study, and the many sources of bias, including publication bias, the apparent desire of journals to publish positive results. Smaller studies, testing multiple variables, and within study flexibility as to designs, outcomes and analyses are all sources of potential problems. Recently a number of investigators have begun to look at “spin” in scientific publications. In a study reviewing over 126 articles on diagnostic performance, a variety of journals with impact factors of 4.0 or greater, 31 % had some form of over-interpretation and a much larger number, perhaps as high as 89%, had some evidence of potential overinterpretation including lack of a sample size calculation, lack of a clear test hypothesis, and failure to report confidence intervals in accuracy measurements. To deal with these issues we will need a multifaceted approach including restructuring the incentives in science, encouraging the publication of high quality studies with negative results, promoting Meta-analysis and creating a culture of ethical scientific research throughout the research community. 

Gary Glazer led the Department of Radiology at Stanford by trying to anticipate where the field was going and be a leader in patient care, education and research. As always changes in the world of Radiology and outside of Radiology provide both challenges and opportunities for us to redefine the field and redefine our mission. This talk will discuss some of the changes under way but also discuss how we can try to achieve that next great “idea” or discovery. The talk will not define what must be done but will try to be a starting point for getting the conversations moving forward.