Reactor: Accelerating Clinical and Translational Research
- Harvard-affiliated researchers who are interested in collaborating with interdisciplinary and cross-institutional investigators around the development of medical advances and improved health outcomes.
- Researchers have the opportunity to develop innovative technologies and methodologies as part of a community that fosters collaboration across the hospitals and Harvard schools. As investigators work on their projects, they receive assistance throughout every stage, to the ultimate goal of developing a solution that impacts patient health.
You have been working with your multi-disciplinary team on a potential solution to a vexing medical challenge that, so far, has few promising developments in the industry. Or, you have a technology that has promising potential to add efficiency to the clinician's work, and improve patient health. What do each of these scenarios need? Support, collaborators, and funding, among other necessities.
In 2013, Reactor was established to respond to the changing needs of clinical and translational researchers, fostering the development of early research through advanced development of a product or discovery that will ultimately create a healthcare solution. In addition to providing incentives and awards to foster cross-disciplinary collaboration and team building, the program makes available project management expertise, skills development, and mentorship to promising teams, projects, and programs.
With the goal of establishing and growing clinical and translational research communities, Reactor launches multiple initiatives each year, inviting researchers to the initial stage, Innovator, and shepherding advanced teams through the later stages of Reactor, called Incubator and Start-Up. As part of Innovator and in partnership with the Harvard Center for Biological Imaging, the program recently launched an RFA for proposals in advanced microscopy/pathology (awardees will be announced in early 2014). As part of Incubator, in January 2014 Reactor will award two investigators each $300,000 in funding for continued work on their initial advanced imaging pilot funding that they received in 2012.
Prevention and Diagnostics
The first two projects chosen for Reactor's Incubator will fund advanced work on imaging solutions that will significantly impact prevention of disease and diagnostics. Giuliano Scarcelli, PhD, and his team are working on an imaging solution using Brillouin imaging to diagnose keratoconus, a degenerative disorder that leads to thinning of the cornea. Scarcelli, an instructor of dermatology at the Wellman Center for Photomedicine at Massachusetts General Hospital (MGH), is working with co-investigators Seok Hyun Yun, PhD, of MGH and Roberto Pineda, MD, from the Massachusetts Eye and Ear.
Since the progression of keratoconus causes debilitating symptoms such as distortion of vision, early detection is critical, and can often save the patient from needing a cornea transplant. One in 2000 people will develop this disorder which often appears in patients as young as fifteen, with a quarter of patients needing a transplant. In addition, if detection does not happen early for patients with keratoconus, they can expect a greater risk of complications if they undergo laser eye surgery. "The biomechanical properties of the cornea are essential for its function," says Scarcelli. "In keratoconus, corneal tissue becomes abnormally weak so that corneal ectasia (thinning and bulging) ensues, causing severe vision degradation. Our instrument aims at measuring corneal strength." In essence, Scarcelli is seeking to answer the question, "Can doctors use this instrument to diagnose keratoconus?"
The Existing Challenges
In a healthy cornea, collagen fibers provide the strength to balance intraocular pressure. When the cornea is weakened, this mechanical balanced is disrupted, which leads to progressive thinning and bulging. Corneal collagen crosslinking (CXL) is a recent development that has been shown to revolutionize the treatment of keratoconus by strengthening corneal stroma. Yet, this technique has been underutilized since adequate diagnosing technology currently does not exist. Often, when keratoconus is diagnosed, patients have less than 400 microns of corneal thickness, which renders CXL useless for treatment.
With their initial pilot funding in 2012, Scarcelli, Yun, and postdoc Sebastien Besner developed a clinical instrument based on Brillouin microscopy that can measure corneal elasticity at high three-dimensional resolution without making contact with the eye. As the team moves forward with advancing this work, they will be introducing elasticity-based metrics for keratoconus and CXL therapy monitoring. They've based their hypothesis on human data during the pilot study, as well as animal data on the CXL procedure.
As Scarcelli and team move forward, they are grateful to Harvard Catalyst not only for the funding support, but for the feedback and input on their project development which helped them outline deliverables and milestones. And most importantly, Scarcelli is experiencing the satisfaction that comes with receiving funding that will allow him to solve a vexing healthcare issue. "It's gratifying to work on a diagnostic tool that could help solve a considerable healthcare problem," he says. "This inspiration provides great incentive, beyond the everyday pressures to publish and apply for grants. These tasks are necessary, but can divert you from these larger goals."
While Scarcelli's project focuses on non-invasive imaging for the eye, the second funded project seeks to change the way brain tumor surgery is currently performed.
Transforming Brain Tumor Resection
As a neurosurgeon, Alexandra Golby, MD, faces a significant challenge each time she performs surgery: resecting a brain tumor without damaging the surrounding healthy tissue. Currently, the best intraoperative imaging technology available for neurosurgery is MRI, which is limiting. "An MRI during surgery is very disruptive to work flow, and by definition, restricted to one look," says Golby, associate professor of neurosurgery and radiology at Harvard Medical School and an associate neurosurgeon at Brigham and Women's Hospital (BWH). "I'm looking to develop surgical tools that will be instrumental in providing real-time feedback, and will ultimately help guide surgeons more accurately."
Often, tumor tissue is not distinguishable from surrounding critical brain tissue during surgery. To prevent damage to healthy tissue, the surgeon may choose to resect less tissue, ultimately leaving the patient with residual disease. And as the surgery progresses, pre-operative imaging becomes inaccurate as deformations occur. This final stage of tumor resection is often the most paramount in preventing injury to surrounding brain tissue, and yet the surgeon has no reliable source of guidance. Post-operative MRIs have shown that in the majority of cases some tumor remnants have been left behind.
Receiving Tissue-Level Information in Real Time
Working with an advanced imaging method called Stimulated Raman scattering (SRS) microscopy that was developed in 2008 by Sunney Xie, Mallinckrodt Professor of Chemistry and Chemical Biology at Harvard University, and co-PI on the current Harvard Catalyst project, Golby and Xie believe this technology has the potential to reliably detect cancerous tissues during surgery. As SRS microscopy allows for high-resolution imaging of tissues, reflecting their macromolecular components (lipids, proteins, DNA), Golby and her team will test this imaging technique on multiple tumor types from different patients. Since brain tumors tend to have tremendous heterogeneity across classes and within grades, the team will employ extensive testing to establish the Raman signal in different brain conditions, including necrosis, gliosis, and post-radiation changes. "SRS will likely change the way neurosurgery is conducted by offering an in situ and label-free imaging modality," says Xie. "We are very encouraged by its potential to make a difference for patients undergoing these procedures."
Bringing the Technology to the Operating Room
Working in the state-of-the-art Advanced Multimodality Image Guided Operating (AMIGO) suite at BWH, where imaging equipment works directly in the operating theater, Golby is planning on eventually setting up the SRS in the facility as part of her Harvard Catalyst project. Staffing a project at this level is one of the challenges investigators face--which is why funding is so important. "In bridging a science technology lab with an operating room, employing the right personnel is key," says Golby. "This funding will allow us to hire people with the skills to understand the complexities of both advanced imaging and neurosurgery."