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Using Imaging to Transform Medicine: Advanced Imaging Pilot Research Grants
Harvard Catalyst sponsored the Advanced Imaging Pilot Research Grants and Concept Development Prizes. The goal was to encourage the Harvard community to develop innovative research projects and ideas that would use advanced imaging technologies (PET, Optical or Physiological MR) to directly address areas of unmet clinical need.
This pilot grant opportunity sought proposals for collaborative, innovative research projects that applied advanced imaging technologies to pressing medical issues. The intent of the Concept Development Prize was to develop speculative and novel ideas that addressed a potential application or evolution of advanced imaging to solve a key medical question. Participation in an Advanced Imaging Symposium was required to be eligible to apply for these funding opportunities.
Funding decisions for the Advanced Imaging funding opportunities were announced in May 2012. Fourteen Pilot Grants were awarded in amounts of up to $50,000 for each one-year project. Four Concept Development prizes were awarded in the amount of $2,000 each.
Robert Brown, MD, Beth Israel Deaconess Medical Center
The increasing incidence of Chronic Kidney Disease (CKD) is leading to a large burden of cardiovascular mortality and renal failure. Kidney fibrosis is considered the final common pathway of renal injury leading to progression of CKD. An MRI technique known as MR elastography (MRE) is able to assess tissue elasticity.This project proposed applying MRE to measure kidney tissue stiffness and if this correlates with renal fibrosis in patients with CKD. If the technique is effective it could become a noninvasive tool for assessing early renal disease, when kidney function is still normal.
Teresa Chen, MD, Massachusetts Eye and Ear Infirmary
The abstract for this grant award has not been published at the request of the Principal Investigator.
Jeffrey Cheng, PhD, Massachusetts Eye and Ear Infirmary
Middle ear disorders constitute a large fraction of patients seen in an otolaryngology practice. Optical coherence tomography (OCT) is a technology that can image cross-sections of soft tissues with a high spatial resolution making it possible to see through the intact eardrum to non-invasively examine the middle ear. This together with a technique called triggered OCT gives the ability to measure the sound induced vibration of the eardrum and the ossicles without damaging the eardrum. The combination of being able to see the middle ear structures and measure the sound vibration of the middle ear using OCT, could be used as a noninvasive diagnostic tool for the diagnosis and management of middle ear disease.
Sylvain Gioux, PhD, Beth Israel Deaconess Medical Center
Lung cancer is the leading cause of cancer death in the United States, accounting for 28% of all cancer deaths. Standard of care for potentially curable lung cancer involves determining the stage of the cancer which is then followed by surgical resection. Using Optical near-Infrared (NIR) fluorescence imaging this project will design and validate a NIR-compatible endoscopic fluorescence imaging system in combination with a fluorescent tracer for intraoperative guidance. Using an animal model, this system will be tested in the laboratory and translated to a pilot human study in lung cancer. This study aims to solve an unmet clinical need and has the potential to impact the management of lung cancer patients.
Alexandra Golby, MD, Brigham and Women’s Hospital
The central objective in brain tumor surgery is to maximize removal of tumor, while sparing adjacent healthy tissue. Despite clear differences on a histologic level, cancerous tissue is often indistinguishable from healthy tissue in the operating room. Stimulated Raman scattering (SRS) microscopy, a cutting-edge imaging method, has the potential to enable surgeons to reliably differentiate cancer-infiltrated tissue from healthy tissue during surgery. SRS microscopy is well suited for intra-operative imaging because it can be performed in situ.
This proposal, will carry out the first SRS imaging of human brain tumor specimens and it will lay the foundation for the integration of SRS as an intra-operative imaging technique to improve the accuracy of brain cancer surgery.
Mukesh Harisinghani, MD, Massachusetts General Hospital
Papillary thyroid cancer (PTC) is the most common type of thyroid cancer. Metastases to the central and lateral neck compartments occur in 20-50% of patients with PTC. Nodal metastases predict disease recurrence and possibly decreased survival in PTC.
High resolution lymphotrophic nanoparticle enhanced magnetic resonance imaging (LNMRI) will be used to determine whether this method can be used to identify metastatic lymph nodes that would not have been noted during surgery. The hope is that this technique will identify small and otherwise undetectable lymph node metastases in patients with PTC.
Jacob Hooker, PhD, Massachusetts General Hospital
Chronic pain is an enormous public health issue, with a prevalence of ~105 million individuals in the US. Until recently, pain disorders have been thought to arise primarily from the dysfunction of nociceptive neurons. Evidence has indicated that micoglial activation (MA) is likely to have a causal role in chronic pain in humans.
A technology that combines Magnetic Resonance/Positron Emission Tomography with a recently developed marker of MA will be used to assess co-localization of MA and to determine the presence of any structural or functional abnormalities. Recognizing the role of microglia in chronic pain would have tremendous clinical implications, including the development of novel pharmacological approaches to pain.
Stephanie Jones, PhD, Boston Children’s Hospital
The incidence of premature birth is high and growing. The ability to save the lives of babies born prematurely is improving each year. However, diagnosis of resulting brain injury is lacking and large numbers of premature children have serious neurodevelopmental disabilities. This proposal will integrate three cutting-edge neuroimaging technologies to develop a novel method to identify the electrophysiological basis of cortical abnormalities in children with periventricular leukomalacia (PVL), a type of brain injury that arises from premature birth.
Eliot Katz, MD, Boston Children’s Hospital
Obstructive sleep apnea (OSA) is a common and serious cause of metabolic, cardiovascular and neurocognitive morbidity in children. This project will use airway MRI data together with computational fluid dynamics to model upper airway flow through a collapsible airway mesh, in order to predict response to surgery. This type of computational modeling technique could determine the optimal surgical and/or medical interventions for OSA and therefore reduce unnecessary procedures and treatment delays.
Anand Kumar, PhD, Massachusetts General Hospital
Head and neck squamous cell carcinoma (HNSCC) is the 6th leading cancer world-wide and results in considerable morbidity and mortality and mandates constant surveillance after treatment, severely impacting the quality of life of patients. CT and MRI are used to assess the extent of disease. surgical resection, together with chemo and radiation therapy, are the main treatments. While these imaging techniques offer high spatial resolution, they have poor contrast for distinguishing tumors from normal tissue.
This project proposes building a new Hybrid Optical X-ray CT (HOX-CT) for the primary diagnosis, intra-operative tumor margin detection, and surveillance after treatment for HNSCC.
Neil Martin, MD, MPH, Brigham and Women’s Hospital
Active surveillance is increasingly recognized as a way to limit morbidity associated with the diagnosis and treatment of low-risk prostate cancer. We currently lack non-invasive imaging modalities to characterize prostate cancer aggressiveness or prognosis for men undergoing active surveillance. Multi-parametric (MP)-MRI has been shown to correlate with physiologic processes and may relate to tumor grade.In this study, the investigators will relate MP-MRI findings to paired biopsy findings to determine whether the MRI can predict un-sampled higher- grade disease. The funding of this pilot grant will be essential in integrating MP-MRI into a developed but not yet opened DF/HCC active surveillance protocol.
Marc Normandin, PhD, Massachusetts General Hospital
Post-mortem analyses detect pancreatic amyloid aggregates in most type-2 diabetes (T2DM) patients, but rarely in type-1 patients and non-diabetics, however the role of amyloidosis in T2DM has yet to be fully understood. This project aims to assess the feasibility of imaging pancreatic amyloid deposits using PET together with an amyloid-targeting radiotracer.
Nisha Sainani MD, Brigham and Women’s Hospital
Definitive diagnosis of early-stage chronic pancreatitis (CP) is difficult due to the inability of conventional imaging techniques to detect early inflammation, and the inability to safely obtain histologic biopsy. This pilot study will evaluate [11C]-D-deprenyl PET/MRI as a non-invasive diagnostic tool for chronic pancreatitis.
Seok-Hyun Yun (Andy), PhD, Massachusetts General Hospital
The biomechanical properties of the cornea are essential for its function. Corneal collagen fibers provide the mechanical strength to withstand intraocular pressure; if the corneal tissue becomes weak, thinning and bulging of the cornea occurs causing severe vision loss. Abnormal weakening of the cornea occurs due to degenerative ocular conditions, e.g. keratoconus, which affects~1/2000 of the general population or as a complication of LASIK surgery. Early detection requires an imaging technique that uses elasticity as a contrast mechanism and this proposal addresses this need by bringing Brillouin imaging to corneal applications. Brillouin imaging can map the elastic modulus of material without contact and with 3D resolution.
A pilot study will be performed to compare normal to keratoconus corneas and normal to post-LASIK corneas. Brillouin imaging has the potential to revolutionize current methods of diagnosis for keratoconus and screening protocols for LASIK surgery.