Abstract: Gene editing with CRISPR technology is transforming biology. Understanding the underlying chemical mechanisms of RNA-guided DNA and RNA cleavage provides a foundation for both conceptual advances and technology development. I will discuss how bacterial CRISPR adaptive immune systems inspire creation of powerful genome editing tools, enabling advances in both fundamental biology and applications in medicine. I will also discuss the ethical challenges of some of these applications with a focus on what our decisions now might mean for future generations.
About: MIPS IMAGinING THE FUTURE seminar series is aimed at catalyzing interdisciplinary discussions in all area of medicine and disease. The seminar series is open and free to everyone in the Stanford community, as well as anyone from the surrounding community, companies or institutions. Our next seminar will host Dr. Jennifer Doudna, Professor of Chemistry, Biochemistry & Molecular Biology, &Li Ka Shing Chancellor’s Professor in Biomedical and Health, University of California, Berkeley; for her presentation on the “World of CRISPR: Editing Genomes and Altering Our Future”.
More Information: http://med.stanford.edu/radiology/imagining-the-future.html
Register: https://www.onlineregistrationcenter.com/JenniferDoudna
“Messaging in the Age of Microtargeting”
John Stafford
Assistant Vice President
Digital Strategy
Stanford University
Bjorn Carey
Senior Director
Digital Strategy
Stanford University
Join via Zoom: https://stanford.zoom.us/j/400566542
Abstract:
Communications has become increasingly data-driven, targeted, and personalized. This has changed how Stanford analyzes communications opportunities from a research perspective and how it engages with relevant audiences. In this presentation, John and Bjorn will share the data and communications strategy underlying three communications initiatives and the resulting execution. They will also provide practical advice for individual thought leadership and communications in this dynamic environment.
About:
John Stafford, MA ’06, is currently Assistant Vice President for Digital Strategy at Stanford, the most senior digital communications role in the university. John is responsible for all aspects of creating a world-class digital communications function: setting the group’s strategy, building analytics and insight programs, counseling on crisis communications, leading multi-channel messaging initiatives, and advising colleagues across the University. He received a Master’s Degree in Communication from Stanford, a B.A. in History from the University of San Francisco, and was a founding advisor to Stanford Medicine X.
Refreshments will be provided.
Muna Aryal Rizal, PhD
Mentor: Jeremy Dahl, PhD and Raag Airan, MD, PhD
Noninvasive Focused Ultrasound Accelerates Glymphatic Transport to Bypass the Blood-Brain Barrier
ABSTRACT
Recent advancement in neuroscience revealed that the Central Nervous System (CNS) comprise glial-cell driven lymphatic system and coined the term called “Glymphatic pathway” by Neuroscientist, Maiden Nedergaard. Furthermore, it has been proven in rodent and non-human primate studies that the glymphatic exchange efficacy can decay in healthy aging, alzheimer’s disease models, traumatic brain injury, cerebral hemorrhage, and stroke. Studies in rodents have also shown that the glymphatic function can accelerate by doing easily-implemented, interventions like physical exercise, changes in body posture during sleep, intake of omega-3 polyunsaturated fatty acids, and low dose alcohol (0.5 g/kg). Here, we proposed for the first time to accelerate the glymphatic function by manipulating the whole-brain ultrasonically using focused ultrasound, an emerging clinical technology that can noninvasively reach virtually throughout the brain. During this SCIT seminar, I will introduce the new ultrasonic approach to accelerates glymphatic transport and will share some preliminary findings.
Eduardo Somoza, MD
Mentor: Sandy Napel, PhD
Prediction of Clinical Outcomes in Diffuse Large B-Cell Lymphoma (DLBCL) Utilizing Radiomic Features Derived from Pretreatment Positron Emission Tomography (PET) Scan
ABSTRACT
Diffuse Large B-Cell lymphoma (DLBCL) is the most common type of lymphoma, accounting for a third of cases worldwide. Despite advancements in treatment, the five-year percent survival for this patient population is around sixty percent. This indicates a clinical need for being able to predict outcomes before the initiation of standard treatment. The approach we will be employing to address this need is the creation of a prognostic model from pretreatment clinical data of DLBCL patients seen at Stanford University Medical Center. In particular, there will be a focus on the derivation of radiomic features from pretreatment positron emission tomography (PET) scans as this has not been thoroughly investigated in similar published research efforts. We will layout the framework for our approach, with an emphasis on the aspects of our design that will allow for the translation of our efforts to multiple clinical settings. More importantly, we will discuss the importance and challenges of assembling a quality clinical database for this type of research. Ultimately, we hope our efforts will lead to the development of a prognostic model that can be utilized to guide treatment in DLBCL patients with refractory disease and/or high risk of relapse after completion of standard treatment.
MIPS Seminar: “Tiny Bubbles, Big Impact: Exploring applications of nanobubbles in ultrasound molecular imaging and therapy”
Agata A. Exner, Ph.D.
Professor of Radiology and Biomedical Engineering
Department of Radiology
Case Western Reserve
Location: Beckman Center, B230
2:00pm – 3:00pm Seminar & Discussion
ABSTRACT
Sub-micron shell stabilized gas bubbles (aka nanobubbles (NB) or ultrafine bubbles) have gained momentum as a robust contrast agent for molecular imaging and therapy using ultrasound. The small size, extended stability and high concentration of nanobubbles make them an ideal tool for new applications of contrast enhanced ultrasound and ultra-
sound-mediated therapy, especially in oncology-related problems. Compared to microbub-bles, nanobubbles can provide superior tumor delineation, identify biomarkers on the vascu-lature and on tumors cells and facilitate drug and gene delivery into tumor tissue. The pat-terns of tissue enhancement under nonlinear ultrasound imaging of nanobubbles are distinct from conventional microbubbles especially in tissues exhibiting vascular hyperper-meability. Specifically, NB kinetics, quantified via time intensity curve analysis, typically show a marked delay in the washout rate and significantly increased area under the curve compared to larger bubbles. This effect is further enhanced by molecular targeting to cellular biomarkers, such as the prostate specific membrane antigen (PSMA) or the receptor protein tyrosine phosphatase, PTPmu. The unique contrast enhancement dynamics of nanobubbles are likely to be a result of direct bubble extravasation and prolonged retention of intact bubbles in target tissue. Thus, understanding the underlying mechanisms behind the unique nanobubble behavior can be the driver of significant future innovations in contrast enhanced ultrasound imaging applications. This presentation will discuss the fundamental challenges with nanobubble formulation and characterization and will showcase how the unique fea-tures of nanobubbles can be leveraged to improve disease detection and treatment using ultrasound.
MIPS Seminar
2:00-2:45 PM | Prof. Pawel Moskal
“Positronium Imaging with the J-PET Scanner”
Head of the Department of Experimental Particle Physics and Applications
Marian Smoluchowski Institute of Physics
Jagiellonian University, 30-348 Krakow, Poland
2:45-3:30 PM | Prof. Ewa Stepien
“Preclinical studies of positronium and extracellular vesicles biomarkers”
Head of the Department of Medical Physics
Marian Smoluchowski Institute of Physics
Jagiellonian University, 30-348 Krakow, Poland
ABSTRACT
As modern medicine develops towards personalized treatment of patients, there is a need for highly specific and sensitive tests to diagnose disease. Our research aims at improvement of specificity of positron emission tomography (PET) in assessment of cancer by use of positronium as a theranostic agent. During PET scanning about 40% of positron annihilations occur through the creation of positronium. “Positronium,” which may be formed in human tissues in the intramolecular spaces, is an exotic atom composed of an electron from tissue and the positron emitted by the radioinuclide. Positronium decay in the patient body is sensitive to the nanostructure and metabolism of human tissues. This phenomenon is not used in present PET diagnostics, yet it is in principle possible to exploit such environment modified properties of positronium as diagnostic biomarkers for cancer assessment. Our first in-vitro studies have shown differences of the positronium mean lifetime and production probability in healthy and cancerous tissues, indicating that they may be used as indicators for in-vivo cancer classification. For the application in medical diagnostics, the properties of positronium atoms need to be determined in a spatially resolved manner. For that purpose we have developed a method of positronium lifetime imaging in which the lifetime and position of positronium atoms are determined on an event-by-event basis. This method requires application of β+ decaying isotope that also emits a prompt gamma ray. We will argue that with total-body PET scanners, the sensitivity of positronium lifetime imaging, which requires coincident registration of the back-to-back annihilation photons and the prompt gamma, is comparable to the sensitivities for metabolic imaging with standard PET scanners.
Our research involves also development of diagnostic methods based on the extracellular vesicles (EVs), which are micro and nano-sized, closed membrane fragments. They are produced by native cells to facilitate the transfer of different signaling factors, structural proteins, nucleic acids or lipids even to distant cells. They are present in all body fluids and they are specific to their parental cells.
Our presentation will be divided into two parts. In the first, the method of positronium imaging and the pilot positronium images obtained with the J-PET detector (the first PET system built based on plastic scintillators) will be reported. This part of the presentation will include also description and perspectives of development of the J-PET technology in view of total-body PET imaging. The second part will concern preliminary results of the preclinical studies of positronium properties in cancerous and healthy tissues sampled from patients as well as in the frozen and living healthy and cancer skin cells in-vitro. The second part will include also description of the novel method for the diagnosis of diabetes and melanoma based on EVs used as biomarkers and drug delivery systems.
References:
P. Moskal, …. E. Ł. Stępień et al., Phys. Med. Biol. 64 (2019) 055017
- Moskal, B. Jasinska, E. Ł. Stępień, S. Bass, Nature Reviews Physics 1 (2019) 527
- Roman M… .E. Ł. Stępień, Nanomedicine 17 (2019) 137
- Ł. Stępień et al., Theranostics 8 (2018) 3874
Hosted by: Craig Levin, Ph.D.
Sponsored by the Molecular Imaging Program at Stanford and the Department of Radiology
Please note this seminar is now cancelled and will be rescheduled for a later date.
MIPS Seminar: Investigating and Imaging key molecular switches associated with Acquirement of Platinum-Taxol resistance in Epithelial Ovarian Cancer
Pritha Ray, Ph.D.
Principal Investigator & Scientific Officer F
Imaging Cell Signaling & Therapeutics Lab
ACTREC, Tata Memorial Center
Navi Mumbai, India
Please note this seminar is now cancelled and will be rescheduled for a future date. Please contact Ashley Williams (ashleylw@stanford.edu) with any questions or concerns. Thank you for your understanding!
IMAGinING THE FUTURE: “Journey Through Academia, Government and Industry: Lessons Learned”
Elias Zerhouni, M.D.
Professor Emeritus
John Hopkins University
“Tumor-Immune Interactions in TNBC Brain Metastases”
Maxine Umeh Garcia, PhD
ABSTRACT: It is estimated that metastasis is responsible for 90% of cancer deaths, with 1 in every 2 advanced staged triple-negative breast cancer patients developing brain metastases – surviving as little as 4.9 months after metastatic diagnosis. My project hypothesizes that the spatial architecture of the tumor microenvironment reflects distinct tumor-immune interactions that are driven by receptor-ligand pairing; and that these interactions not only impact tumor progression in the brain, but also prime the immune system (early on) to be tolerant of disseminated cancer cells permitting brain metastases. The main goal of my project is to build a model that recapitulates tumor-immune interactions in brain-metastatic triple-negative breast cancer, and use this model to identify novel druggable targets to improve survival outcomes in patients with devastating brain metastases.
“Classification of Malignant and Benign Peripheral Nerve Sheath Tumors With An Open Source Feature Selection Platform”
Michael Zhang, MD
ABSTRACT: Radiographic differentiation of malignant peripheral nerve sheath tumors (MPNSTs) from benign PNSTs is a diagnostic challenge. The former is associated with a five-year survival rate of 30-50%, and definitive management requires gross total surgical with wide negative margins in areas of sensitive neurologic function. This presentation describes a radiomics approach to pre-operatively identifying a diagnosis, thereby possibly avoiding surgical complexity and debilitating symptoms. Using an open-source, feature extraction platform and machine learning, we produce a radiographic signature for MPNSTs based on routine MRI.
ZOOM LINK HERE
“High Resolution Breast Diffusion Weighted Imaging”
Jessica McKay, PhD
ABSTRACT: Diffusion-weighted imaging (DWI) is a quantitative MRI method that measures the apparent diffusion coefficient (ADC) of water molecules, which reflects cell density and serves as an indication of malignancy. Unfortunately, however, the clinical value of DWI is severely limited by the undesirable features in images that common clinical methods produce, including large geometric distortions, ghosting and chemical shift artifacts, and insufficient spatial resolution. Thus, in order to exploit information encoded in diffusion characteristics and fully assess the clinical value of ADC measurements, it is first imperative to achieve technical advancements of DWI.
In this talk, I will largely focus on the background of breast DWI, providing the clinical motivation for this work and explaining the current standard in breast DWI and alternatives proposed throughout the literature. I will also present my PhD dissertation work in which a novel strategy for high resolution breast DWI was developed. The purpose of this work is to improve DWI methods for breast imaging at 3 Tesla to robustly provide diffusion-weighted images and ADC maps with anatomical quality and resolution. This project has two major parts: Nyquist ghost correction and the use of simultaneous multislice imaging (SMS) to achieve high resolution. Exploratory work was completed to characterize the Nyquist ghost in breast DWI, showing that, although the ghost is mostly linear, the three-line navigator is unreliable, especially in the presence of fat. A novel referenceless ghost correction, Ghost/Object minimization was developed that reduced the ghost in standard SE-EPI and advanced SMS. An advanced SMS method with axial reformatting (AR) is presented for high resolution breast DWI. In a reader study, AR-SMS was preferred by three breast radiologists compared to the standard SE-EPI and readout-segmented-EPI.
“Machine-learning Approach to Differentiation of Benign and Malignant Peripheral Nerve Sheath Tumors: A Multicenter Study”
Michael Zhang, MD
ABSTRACT: Clinicoradiologic differentiation between benign and malignant peripheral nerve sheath tumors (PNSTs) is a diagnostic challenge with important management implications. We sought to develop a radiomics classifier based on 900 features extracted from gadolinium-enhanced, T1-weighted MRI, using the Quantitative Imaging Feature Pipeline and the PyRadiomics package. Additional patient-specific clinical variables were recorded. A radiomic signature was derived from least absolute shrinkage and selection operator, followed by gradient boost machine learning. A training and test set were selected randomly in a 70:30 ratio. We further evaluated the performance of radiomics-based classifier models against human readers of varying medical-training backgrounds. Following image pre-processing, 95 malignant and 171 benign PNSTs were available. The final classifier included 21 features and achieved a sensitivity 0.676, specificity 0.882, and area under the curve (AUC) 0.845. Collectively, human readers achieved sensitivity 0.684, specificity 0.742, and AUC 0.704. We concluded that radiomics using routine gadolinium enhanced, T1-weighted MRI sequences and clinical features can aid in the evaluation of PNSTs, particularly by increasing specificity for diagnosing malignancy. Further improvement may be achieved with incorporation of additional imaging sequences.
MIPS Seminar Series: Translational Opportunities in Glycoscience
Carolyn Bertozzi, PhD
Director, ChEM-H
Anne T. and Robert M. Bass Professor in the School of Humanities and Sciences
Professor, by courtesy, of Chemical and Systems Biology
Stanford University
Location: Zoom
Webinar URL: . https://stanford.zoom.us/j/94010708043
Dial: US: +1 650 724 9799 or +1 833 302 1536 (Toll Free)
Webinar ID: 940 1070 8043
Passcode: 659236
12:00pm – 12:45pm Seminar & Discussion
RSVP Here
ABSTRACT
Cell surface glycans constitute a rich biomolecular dataset that drives both normal and pathological processes. Their “readers” are glycan-binding receptors that can engage in cell-cell interactions and cell signaling. Our research focuses on mechanistic studies of glycan/receptor biology and applications of this knowledge to new therapeutic strategies. Our recent efforts center on pathogenic glycans in the tumor microenvironment and new therapeutic modalities based on the concept of targeted degradation.
ABOUT
Carolyn Bertozzi is the Baker Family Director of Stanford ChEM-H and the Anne T. and Robert M. Bass Professor of Humanities and Sciences in the Department of Chemistry at Stanford University. She is also an Investigator of the Howard Hughes Medical Institute. Her research focuses on profiling changes in cell surface glycosylation associated with cancer, inflammation and infection, and exploiting this information for development of diagnostic and therapeutic approaches, most recently in the area of immuno-oncology. She is an elected member of the National Academy of Medicine, the National Academy of Sciences, and the American Academy of Arts and Sciences. She also has been awarded the Lemelson-MIT Prize, a MacArthur Foundation Fellowship, the Chemistry for the Future Solvay Prize, among many others.
Hosted by: Katherine Ferrara, PhD
Sponsored by: Molecular Imaging Program at Stanford & the Department of Radiology