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.

Portable real-time optical coherence tomography system for intraoperative imaging and staging of breast cancer

Breast cancer continues to be one of the most widely diagnosed forms of cancer amongst women and the second leading type of cancer deaths amongst women. The recurrence rate of breast cancer is highly dependent on several factors including the complete removal of the primary tumor and the presence of cancer cells in involved lymph nodes. The metastatic spread and staging of breast cancer is also evaluated through the nodal assessment of the regional lymphatic system. A portable real-time spectral domain optical coherence tomography system is being presented as a clinical diagnostic tool in the intraoperative delineation of tumor margins as well as for real time lymph node assessment. The system employs a super luminescent diode centered at 1310 nm with a bandwidth of 92 nm. Using a spectral domain detection system, the data is acquired at a rate of 5 KHz / axial scan. The sample arm is a galvanometer scanning telecentric probe with an objective lens (f = 60 mm, confocal parameter = 1.5 mm) yielding an axial resolution of 8.3 μm and a transverse resolution of 35.0 μm. Images of tumor margins are acquired in the operating room ex vivo on freshly excised human tissue specimen. This data shows the potential of the use of OCT in defining the structural tumor margins in breast cancer. Images taken from ex-vivo samples on the bench system clearly delineate the differences between clusters of tumor cells and nearby adipose cells. In addition, the data shows the potential for OCT as a diagnostic tool in the staging of cancer metastasis through locoregional lymph node assessment.

Needle-probe system for the measurement of tissue refractive index

Needle-based devices, which are in wide clinical use for needle biopsy procedures, may be augmented by suitable optical techniques for the localization and diagnosis of diseased tissue. Tissue refractive index is one optical contrast mechanism with diagnostic potential. In the case of mammary tissue, for example, recent research indicates that refractive index variations between tissue types may be useful for the identification of cancerous tissue. While many coherence-based forward-sensing devices have been developed to detect scattering changes, none have demonstrated refractive index measurement capabilities. We present a novel needle-based device that is capable of simultaneously measuring refractive index and scattering. Coupled to the sample arm of an optical coherence tomography system, the needle device detects the scattering response and optical pathlength through tissue residing in a fixed-width channel. Near-infrared measurements of tissues and materials with known optical properties using a prototype device will be presented. This work demonstrates the feasibility of integrated in vivo measurement of refractive index and scattering in conjunction with existing clinical needle-based devices.

Interferometric synthetic aperture microscopy
Publication

Interferometric synthetic aperture microscopy

State-of-the-art methods in high-resolution three-dimensional optical microscopy require that the focus be scanned through the entire region of interest. However, an analysis of the physics of the light-sample interaction reveals that the Fourier-space coverage is independent of depth. Here we show that, by solving the inverse scattering problem for interference microscopy, computed reconstruction yields volumes with a resolution in all planes that is equivalent to the resolution achieved only at the focal plane for conventional high-resolution microscopy. In short, the entire illuminated volume has spatially invariant resolution, thus eliminating the compromise between resolution and depth of field. We describe and demonstrate a novel computational image-formation technique called interferometric synthetic aperture microscopy (ISAM). ISAM has the potential to broadly impact real-time three-dimensional microscopy and analysis in the fields of cell and tumour biology, as well as in clinical diagnosis where imaging is preferable to biopsy.