One of the Exciting Advancements Being Funded by the Ivy Foundation

Scientists create nanoparticles that home in on brain tumor, increasing accuracy of surgical removal

BY BRUCE GOLDMAN

Renee Reijo PeraSam Gambhir

Like special-forces troops laser-tagging targets for a bomber pilot, tiny particles that can be imaged three different ways at once have enabled Stanford University School of Medicine scientists to remove brain tumors from mice with unprecedented accuracy.

In a study published online April 15 in Nature Medicine, a team led by Sam Gambhir, MD, PhD, professor and chair of radiology, showed that the minuscule nanoparticles engineered in his lab homed in on and highlighted brain tumors, precisely delineating their boundaries and greatly easing their complete removal. The new technique could someday help improve the prognosis of patients with deadly brain cancers.

About 14,000 people are diagnosed annually with brain cancer in the United States. Of those cases, about 3,000 are glioblastomas, the most aggressive form of brain tumor. The prognosis for glioblastoma is bleak: the median survival time without treatment is three months. Surgical removal of such tumors — a virtual imperative whenever possible — prolongs the typical patient’s survival by less than a year. One big reason for this is that it is almost impossible for even the most skilled neurosurgeon to remove the entire tumor while sparing normal brain.

“With brain tumors, surgeons don’t have the luxury of removing large amounts of surrounding normal brain tissue to be sure no cancer cells are left,” said Gambhir, who is the Virginia and D.K. Ludwig Professor for Clinical Investigation in Cancer Research and director of the Molecular Imaging Program at Stanford. “You clearly have to leave as much of the healthy brain intact as you possibly can.”

This is a real problem for glioblastomas, which are particularly rough-edged tumors. In these tumors, tiny fingerlike projections commonly infiltrate healthy tissues, following the paths of blood vessels and nerve tracts. An additional challenge is posed by micrometastases: minuscule tumor patches caused by the migration and replication of cells from the primary tumor. Micrometastases dotting otherwise healthy nearby tissue but invisible to the surgeon’s naked eye can burgeon into new tumors.

Although brain surgery today tends to be guided by the surgeon’s naked eye, new molecular imaging methods could change that, and this study demonstrates the potential of using high-technology nanoparticles to highlight tumor tissue before and during brain surgery.

The nanoparticles used in the study are essentially tiny gold balls coated with imaging reagents. Each nanoparticle measures less than five one-millionths of an inch in diameter — about one-sixtieth that of a human red blood cell.

“We hypothesized that these particles, injected intravenously, would preferentially home in on tumors but not healthy brain tissue,” said Gambhir, who is also a member of the Stanford Cancer Institute. “The tiny blood vessels that feed a brain tumor are leaky, so we hoped that the spheres would bleed out of these vessels and lodge in nearby tumor material.” The particles’ gold cores, enhanced as they are by specialized coatings, would then render the particles simultaneously visible to three distinct methods of imaging, each contributing uniquely to an improved surgical outcome.

One of those methods, magnetic resonance imaging, is already frequently used to give surgeons an idea of where in the brain the tumor resides before they operate. MRI is well-equipped to determine a tumor’s boundaries, but when used preoperatively it can’t perfectly describe an aggressively growing tumor’s position within a subtly dynamic brain at the time the operation itself takes place.

The Gambhir team’s nanoparticles are coated with gadolinium, an MRI contrast agent, in a way that keeps them stably attached to the relatively inert spheres in a blood-like environment. (In a2011 study published in Science Translational Medicine, Gambhir and his colleagues showed in small animal models that nanoparticles similar to those used in this new study, but not containing gadolinium, were nontoxic.)

A second, newer method is photoacoustic imaging, in which pulses of light are absorbed by materials such as the nanoparticles’ gold cores. The particles heat up slightly, producing detectable ultrasound signals from which a three-dimensional image of the tumor can be computed. Because this mode of imaging has high depth penetration and is highly sensitive to the presence of the gold particles, it can be useful in guiding removal of the bulk of a tumor during surgery.

The third method, called Raman imaging, leverages the capacity of certain materials (included in a layer coating the gold spheres) to give off almost undetectable amounts of light in a signature pattern consisting of several distinct wavelengths. The gold cores’ surfaces amplify the feeble Raman signals so they can be captured by a special microscope.

To demonstrate the utility of their approach, the investigators first showed via various methods that the lab’s nanoparticles specifically targeted tumor tissue, and only tumor tissue.

Next, they implanted several different types of human glioblastoma cells deep into the brains of laboratory mice. After injecting the imaging-enhancing nanoparticles into the mice’s tail veins, they were able to visualize, with all three imaging modes, the tumors that the glioblastoma cells had spawned.

The MRI scans provided good preoperative images of tumors’ general shapes and locations. And during the operation itself, photoacoustic imaging permitted accurate, real-time visualization of tumors’ edges, enhancing surgical precision.

But neither MRI nor photoacoustic imaging by themselves can distinguish healthy from cancerous tissue at a sufficiently minute level to identify every last bit of a tumor. Here, the third method, Raman imaging, proved crucial. In the study, Raman signals emanated only from tumor-ensconced nanoparticles, never from nanoparticle-free healthy tissue. So, after the bulk of an animal’s tumor had been cleared, the highly sensitive Raman-imaging technique was extremely accurate in flagging residual micrometastases and tiny fingerlike tumor projections still holed up in adjacent normal tissue that had been missed on visual inspection. This, in turn, enabled these dangerous remnants’ removal.

“Now we can learn the tumor’s extent before we go into the operating room, be guided with molecular precision during the excision procedure itself and then immediately afterward be able to ‘see’ once-invisible residual tumor material and take that out, too,” said Gambhir, who suggested that the nanoparticles’ propensity to heat up on photoacoustic stimulation, combined with their tumor specificity, might also make it possible for them to be used to selectively destroy tumors. He also expressed optimism that this kind of precision could eventually be brought to bear on other tumor types.

The study was funded by the National Institutes of Health, the National Cancer Institute’s Center for Cancer Nanotechnology Excellence, the Ben and Catherine Ivy Foundation, the Canary Foundation and the Leon Levy Foundation.

Sharing first authorship were Moritz Kircher, MD, PhD, and postdoctoral scholar Adam de La Zerda, PhD. Some of the animal work was carried out through a collaboration with researchers at Memorial Sloan-Kettering Cancer Center (where Kircher is now employed) and at Weill-Cornell Medical College, both in New York City. Additional Stanford co-authors were postdoctoral scholars Jesse Jokerst, PhD, and Cristina Zavaleta, PhD; clinical instructor Erik Mitra, MD, PhD; and research scientist Frezghi Habte, PhD, all of the Department of Radiology; and Robert Sinclair, PhD, professor and chair of materials science and engineering in the School of Engineering, and his graduate student Paul Kempen.

Information about the medical school’s Department of Radiology, which also supported the work, is available at http://radiology.stanford.edu/.

Good Advice for Everyone

HOW TO PREVENT BRAIN CANCER

Sep 2, 2010 | By Lee Francis
How to Prevent Brain Cancer

Photo Credit blue brain image by John Sfondilias from Fotolia.com
Brain cancer is a condition in which malignant tumors develop within the brain. The tumor can originate in the brain or travel to the brain from other parts of the body. Malignant brain tumors contain cancer cells. Most invade surrounding tissues and are fast growing. The causes of primary brain cancers are unknown. However, the best best way to prevent brain cancer is to live a healthy lifestyle and avoid at risk factors that may cause the disease.

Step 1

Avoid exposure to certain environmental agents. For example, vinyl chloride is an established risk factor for brain cancer. Sometimes, areas located near manufacturing and chemical plants emit chemicals into the air. According to the American Cancer Association, therapeutic radiation exposure to the head is considered a major cause of childhood cancer. Children were previously treated with low dose radiation for certain conditions which increased their risk for brain tumors. The American Cancer Society adds that radiation treatment for other cancers may lead to brain tumors because radiation for minor conditions are no longer used in children or adults.

Step 2

Eat a healthy diet. Include foods high in Omega-3 fatty acids such as fish and lean meats. In addition, vegetables and fruits like broccoli, beans, spinach, apples, oranges and pineapples are rich in antioxidants, which work to prevent cancer and a host of other diseases. They are also packed with vitamins to promote healthy brain and body functions. According to the American Cancer Society, a diet high in vegetables and fruits has been linked to the reduction of certain cancers.

Step 3

Visit your doctor regularly. Annual physicals are important, especially if you are experiencing abnormal signs or symptoms. In addition, doctors are trained to search for brain cancer symptoms. The National Institute of Neurological Disorders reports that identifying a brain tumor in the early stages is important to fighting and recovering from brain cancer.

Step 4

Limit your consumption of alcohol. According to the University of Maryland Medical Center, excessive drinking and smoking can lead to certain diseases that may put a person at risk for cancer. Metastic brain tumors being in other parts of the body and spread to the brain through the bloodstream. For example, if a person develops lung cancer from smoking, its possible that the cancer can spread and work its way to the brain. Excessive drinking can also lead to liver diseases that can also spread to the brain as well.

http://www.livestrong.com/article/224692-how-to-prevent-brain-cancer/#ixzz2BlTDPu1A

Congratulations to Our Partners at Swedish Medical Center

Swedish Medical Center Foundation Raises $100 Million to Help Meet Increasing Demand for Regional Health-Care Services

The Campaign for Swedish initiative exceeds fund-raising goal during challenging economic times; Initial $100 million campaign goal reached 18 months early

SEATTLE, Oct. 26, 2012 /PRNewswire/ — Swedish Medical Center’s seven-year fund-raising initiative, called The Campaign for Swedish, has raised $103 million, exceeding its initial $100 million fund-raising goal in approx. five-and-a-half years.  The Campaign, launched to help improve patient care and treatment options throughout the Swedish system, is the largest fund-raising effort undertaken by the private, non-profit health system to date.

“We launched this Campaign with the vision of creating the region’s first broad-based, full-service, non-profit health system that is nationally and internationally known for providing exceptional care,” said Janet True, co-chair of the Campaign Leadership Council. “Raising $100 million in seven years seemed ambitious seven years ago, and we have been humbled by the community’s generosity in helping us exceed our initial goal more than a year and a half ahead of schedule.”

More than 50,000 community members have contributed to The Campaign for Swedish to date. The Swedish Medical Center Foundation, the fundraising arm of the hospital, has had five consecutive record-breaking years, bolstered by $11.8 millionraised from Swedish physicians and 26 gifts of $1 million or more during a period when many non-profit health-care organizations have struggled to maintain contributions.

“Swedish has a long history as one of our region’s premier health-care delivery systems,” said Campaign Co-Chair Dave Sabey. During a challenging time for health care in the United States, we are fortunate to count on the community’s generous investment to ensure that Swedish continues to deliver outstanding health care for all those who need it in the Puget Sound region.”

More than 40 Major Initiatives Supported to Date

The Campaign for Swedish has funded more than 40 major programs and projects at Swedish. Major priorities supported by the Campaign include:

  • Cancer: $18.8 million has been given by the community to advance treatment, buy new technology, support research and develop new facilities within the Swedish Cancer Institute. The new True Family Women’s Cancer Center is a direct result of this effort, as is the Breast Care Express.
  • Neuroscience: $16.7 million has been directed to the Swedish Neuroscience Institute to support facilities and technology upgrades, and to establish two state-of-the-art centers for the treatment of brain tumors and multiple sclerosis: the Ben & Catherine Ivy Center for Advanced Brain Tumor Treatment and the new Swedish MS Center.
  • Heart & Vascular: $12 million for the Swedish Heart & Vascular Institute has been given to endow medical directorships, launch capital projects, advance clinical research, and support patient education as well as outreach programs. These funds supported the comprehensive heart failure program and expanded our cardiac clinical research program.
  • Community Health: $10.4 million to advance community health initiatives at Swedish to provide quality health care to the growing number of uninsured and underinsured members of our community. Among the major community health programs supported by the Campaign is the Swedish Community Specialty and Dental Clinic, a specialty care center that provides surgical and specialty care – including specialty dental care – at no cost to low-income uninsured and underinsured patients.
  • Pediatrics and Women and Infants: $5 million was given by the community to provide program support to moms and babies as well as pediatric programs at Swedish. The Gossman Center for Advanced Healthcare Simulation and the expanded Neonatal Intensive Care Unit at Swedish/First Hill were direct benefactors of these funds, as was pediatric therapy and child life services.

Campaign Fundraising to Continue through December 2013

During the next 15 months, the Swedish Medical Center Foundation will continue to partner with hospital and Campaign leadership to raise additional funds for new and existing programs, including the True Family Women’s Cancer Center, the MS Center at Swedish, the Ivy Center for Advanced Brain Tumor Treatment, and the Comprehensive Heart Failure Program.

Support generated during the “Campaign Homestretch” is also needed to support new initiatives, such as the creation of a new postpartum wellness and education center that will meet the increased patient demand for Swedish services. The Lytle Center, named for a generous $1 million lead gift from Chuck and Karen Lytle, will provide state-of-the-art outpatient follow-up care and support for new babies and mothers in a large, accessible and welcoming space at the First Hill campus.

“We are so grateful for this community’s overwhelming support of The Campaign for Swedish in allowing us to advance health care for more than 2,000,000 patients,” said Swedish Foundation’s Executive Director Don Theophilus. “Having raised more than $3 million beyond our initial $100 million campaign goal in less than six years is very exciting, but we’re not declaring victory yet. There is still much work which needs to be done.”

About ‘The Campaign for Swedish’

The Swedish Medical Center Foundation launched The Campaign for Swedish in January 2007 in conjunction with the Swedish Medical Center Foundation board and a 17-person volunteer Campaign Leadership Council lead by co-chairs Janet True, Kirby McDonald and Dave Sabey. More information can be found online at www.campaignforswedish.org.

About Swedish

Swedish has grown over the last 102 years to become the largest non-profit health provider in the Greater Seattle area with 11,000 employees, more than 2,000 physicians and 1,700 volunteers. It is comprised of five hospital campuses (First Hill,Cherry Hill, Ballard, Edmonds and Issaquah); ambulatory care centers in Redmond and Mill Creek; and Swedish Medical Group, a network of more than 100 primary-care and specialty clinics located throughout the Greater Puget Sound area. In addition to general medical and surgical care including robotic-assisted surgery, Swedish is known as a regional referral center, providing specialized treatment in areas such as cardiovascular care, cancer care, neuroscience, orthopedics, high-risk obstetrics, pediatric specialties, organ transplantation and clinical research. For more information, visit www.swedish.org,www.swedishcares.orgwww.facebook.com/swedishmedicalcenter, or www.twitter.com/swedish.

Swedish is affiliated with Providence Health & Services, which is a Catholic, not-for-profit organization founded by the Sisters of Providence in 1856 with 27 hospitals, 214 physician clinics and almost 53,000 employees across five states. Based in Renton, Wash., Providence Health & Services provides strategic and management services to integrated health-care systems inAlaska, California, Montana, Oregon and Washington state. For more information, visit www.providence.org.

 

http://www.prnewswire.com/news-releases/swedish-medical-center-foundation-raises-100-million-to-help-meet-increasing-demand-for-regional-health-care-services-175959741.html