Research Fellow @ Massachusetts Institute of Technology, Transfusion Medicine Fellow @ Dartmouth-Hitchcock Medical Center

Nonprofit World

NONPROFIT WORLD
IN THIS TOGETHER. Freddy Nguyen had such a hard time learning about M.D./Ph.D. programs that he vowed to help other applicants avoid a similar fate. Last month, the organization that grew out of his frustration, the American Physician Scientists Association (APSA), hosted its fourth annual meeting in Chicago. The group is doing well enough for the 26-year-old Nguyen, an M.D./Ph.D. candidate at the University of Illinois, Urbana-Champaign, to step down as president and hand the reins to the next generation. APSA (www.physicianscientists.org) has more than 1000 student members from about 120 medical schools. It organizes national and regional conferences each year where this rare breed—who face a 10-to-14-year slog—can meet fellow students, present their research, and learn from senior investigators who have traveled the same path “It’s really about connecting people across organizations,” says Nguyen. “Freddy has a remarkable passion for this,” says Joseph Bast, director of the M.D./Ph.D. program at the University of Kansas Medical Center, who calls the group “a very worthwhile organization.” The new president is James Pauff, who attends Ohio State University in Columbus.

Coherent optical imaging and guided interventions in breast cancer: translating technology into clinical applications

Breast cancer continues to be one of the most widely diagnosed forms of cancer in women and the second leading type of cancer deaths for women. The metastatic spread and staging of breast cancer is typically evaluated through the nodal assessment of the regional lymphatic system, and often this is performed during the surgical resection of the tumor mass. The recurrence rate of breast cancer is highly dependent on several factors including the complete removal of the primary tumor during surgery, and the presence of cancer cells in involved lymph nodes. Hence, developing means to more accurately resect tumor cells, along with the tumor mass, and ensure negative surgical margins, offers the potential to impact outcomes of breast cancer. The use of diffuse optical tomography has been applied for screening optical mammography applications as an alternative to standard x-ray mammography. The use of coherence ranging and coherent optical imaging in breast tissue has also found numerous applications, including intra-operative assessment of tumor margin status during lumpectomy procedures, assessment of lymph node changes for staging metastatic spread, and for guiding needle-biopsy procedures. The development, pre-clinical testing, and translation of techniques such as low-coherence interferometry (LCI) and optical coherence tomography (OCT) into clinical applications in breast cancer is demonstrated in these feasibility studies.

Publication

The birth of the American Physician Scientists Association–the next generation of Young Turks

The American Society for Clinical Investigation (ASCI) was started a century ago to foster and to address the needs of the younger physician-scientists. A hundred years later, ASCI remains one of the premier organizations for physician-scientists and one of most well-respected organizations in the medical community. I have had the opportunity and pleasure to interact with the ASCI not only as an organization through my tenure as president of the American Physician Scientists Association, but also with its members over the last four years. In my view, the same characteristics that permeate ASCI the organization also define ASCI the membership–mentorship, exemplary role models, advocacy, and leadership.

Publication

Medical Student Attitudes and Perceptions on the USMLE Review

Student feedback on the proposed changes to the USMLE
Since the formation of the Committee to Evaluate the USMLE Program (CEUP), several avenues have been made available for students to provide feedback. One of those avenues have been through a student representative to CEUP who has jointly appointed by the leaders of the American Medical Student Association (AMSA), the American Medical Association – Medical Student Section (AMA-MSS), and the Association of American Medical Colleges – Organization of Student Representatives (AAMC-OSR). Student feedback, at the time, had been largely limited to the input from the leaderships of the aforementioned organizations who were primarily surveyed by the NBME. Subsequently, students were also given the opportunity to participate in focus groups and on an electronic message board (http://usmle.org/comprev). In addition to these opportunities, the American Physician Scientists Association (APSA) felt that there was a paucity of quantitative, objective data aimed at gathering broad student feedback; therefore, APSA undertook the initiative to develop a national survey intended to gauge medical student sentiment in an effort to further help shape and support the dialogue surrounding the Comprehensive Review of the USMLE.

Magnetic protein microspheres as dynamic contrast agents for magnetomotive optical coherence tomography

Optical coherence tomography (OCT) is an emerging biomedical imaging modality that has been developed over the last 15 years. More recently, OCT has been used for the intraoperative imaging of tumor margins in breast cancer and axillary lymph nodes providing a real time in-vivo assessment of the tissue morphology. Traditional OCT images are limited by only being able to observe morphological structures. As diagnostic medicine continues to push for earlier detection, one must develop functional imaging modalities that would detect molecular information in-vivo allowing a real-time microscopic analysis of the tissue specimen. A novel modality of OCT called magnetomotive-OCT (MMOCT) has been developed by our group, employing an induced modulated magnetic field with a magnetic contrast agent to create the added contrast to structural OCT images. Modified protein microspheres with a BSA protein shell functionalized with RGD peptide sequences for targeting and an oil core have been designed and synthesized. Magnetic nanoparticles (Fe3O4) and Nile Red dye have been encapsulated into its oil core. These microspheres have previously been demonstrated to target cancer cells by functionalizing them with a layer of RGD peptides and could be functionalized with monoclonal antibodies. Preliminary results show that these magnetic microspheres, which are 2.0- 5.0 microns in size, are readily detectable under MM-OCT when embedded in a 5% agarose gel, in a 3-D scaffold of macrophage cells previously incubated with the microspheres, and when injected in-vivo into a tumor from an NMUcarcinogen rat animal model for breast cancer.

Publication

Association of Professors of Medicine Physician-Scientist Initiative: Recommendations for Revitalizing the Nation’s Physician-Scientist Workforce

Physician-scientists, because of their perspective of asking scientific questions influenced by their experience of caring for patients, are uniquely positioned to perform research that directly benefits patients. Yet, the physician-scientist workforce is shrinking and aging, portending decreases in the effectiveness of the medical enterprise to discover new treatments and cures. Recognizing the detrimental effects of a physician-scientist shortage, the Association of Professors of Medicine (APM)—the organization of departments of internal medicine represented by chairs and appointed leaders at medical schools and affiliated teaching hospitals in the United States and Canada—has begun a long-term initiative to identify, develop, and implement substantive and practical solutions that will ensure the survival, growth, and diversity of the physician-scientist workforce.

The APM Physician-Scientist Initiative—led by Principal Investigator Andrew I. Schafer, MD—is planned in linked phases. Phase I focused on evaluating the physician-scientist problem and creating a set of recommendations for growing, revitalizing, and diversifying the physician-scientist workforce. This goal was achieved through a series of structured surveys and focus groups (results summarized in Appendix A), which in turn helped inform the agenda for the APM Physician-Scientist Initiative Consensus Conference, “Revitalization of the Nation’s Physician-Scientist Workforce,” in November 2007. The consensus conference (planning committee, Appendix B) assembled leaders of the academic, medical, and research communities; representatives from the various governing bodies that influence, fund, and regulate biomedical research and academia; respected experts on issues facing the physician-scientist workforce; and young physician-scientists (conference participants are listed in Appendix C).

Following plenary lectures presenting the perspectives of academia, industry, and the federal government, the conference was largely interactive, with targeted breakout groups focused on specific aspects of the physician scientist career path (see Appendix D). Breakout group participants proposed their single, best, articulated recommendation for enhancing the highlighted areas, while the full group debated and discussed additional opportunities to improve the pipeline, whether via entry or improved retention. The complete list of 30 recommendations emanating from the conference breakout sessions and general group discussions is provided—in no priority order—in Appendix E. Participants provided a preliminary assessment of the recommendations followed by a more detailed, analytical assessment post-conference, prioritizing, commenting, and editing the recommendations to create a more sharply focused action plan.

While Phase I of the initiative was intended to understand the driving contemporary forces that shape the problem today and to formulate specific recommendations, Phase II will expand and activate a coalition group of key leadership organizations to move the agenda forward by developing next steps, a coordinated national strategy, and oversight of implementation of the action plan.

Publication

Optical coherence tomography: a review of clinical development from bench to bedside

Since its introduction, optical coherence tomography (OCT) technology has advanced from the laboratory bench to the clinic and back again. Arising from the fields of low coherence interferometry and optical time- and frequency-domain reflectometry, OCT was initially demonstrated for retinal imaging and followed a unique path to commercialization for clinical use. Concurrently, significant technological advances were brought about from within the research community, including improved laser sources, beam delivery instruments, and detection schemes. While many of these technologies improved retinal imaging, they also allowed for the application of OCT to many new clinical areas. As a result, OCT has been clinically demonstrated in a diverse set of medical and surgical specialties, including gastroenterology, dermatology, cardiology, and oncology, among others. The lessons learned in the clinic are currently spurring a new set of advances in the laboratory that will again expand the clinical use of OCT by adding molecular sensitivity, improving image quality, and increasing acquisition speeds. This continuous cycle of laboratory development and clinical application has allowed the OCT technology to grow at a rapid rate and represents a unique model for the translation of biomedical optics to the patient bedside. This work presents a brief history of OCT development, reviews current clinical applications, discusses some clinical translation challenges, and reviews laboratory developments poised for future clinical application.

Publication

Multimodal biomedical imaging with asymmetric single-walled carbon nanotube/iron oxide nanoparticle complexes

Magnetic iron oxide nanoparticles and near-infrared (NIR) fluorescent single-walled carbon nanotubes (SWNT) form heterostructured complexes that can be utilized as multimodal bioimaging agents. Fe catalyst-grown SWNT were individually dispersed in aqueous solution via encapsulation by oligonucleotides with the sequence d(GT)15, and enriched using a 0.5 T magnetic array. The resulting nanotube complexes show distinct NIR fluorescence, Raman scattering, and visible/NIR absorbance features, corresponding to the various nanotube species. AFM and cryo-TEM images show DNA-encapsulated complexes composed of a approximately 3 nm particle attached to a carbon nanotube on one end. X-ray diffraction (XRD) and superconducting quantum interference device (SQUID) measurements reveal that the nanoparticles are primarily Fe2O3 and superparamagnetic. The Fe2O3 particle-enriched nanotube solution has a magnetic particle content of approximately 35 wt %, a magnetization saturation of approximately 56 emu/g, and a magnetic relaxation time scale ratio (T1/T2) of approximately 12. These complexes have a longer spin-spin relaxation time (T2 approximately 164 ms) than typical ferromagnetic particles due to the smaller size of their magnetic component while still retaining SWNT optical signatures. Macrophage cells that engulf the DNA-wrapped complexes were imaged using magnetic resonance imaging (MRI) and NIR mapping, demonstrating that these multifunctional nanostructures could potentially be useful in multimodal biomedical imaging.

Publication

Needle-based refractive index measurement using low-coherence interferometry

We present a novel needle-based device for the measurement of refractive index and scattering using low-coherence interferometry. Coupled to the sample arm of an optical coherence tomography system, the device detects the scattering response of, and optical path length through, a sample residing in a fixed-width channel. We report use of the device to make near-infrared measurements of tissues and materials with known optical properties. The device could be used to exploit the refractive index variations of tissue for medical and biological diagnostics accessible by needle insertion.

Physician-scientist with extensive experience developing and translating nanotechnologies and biomedical optical technologies from the bench to clinic in areas of genetics, oncology, and cardiovascular diseases. Extensive experience in community building in healthcare innovation, research, medical, and physician-scientist communities through various leadership roles.

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