Dr. Lawrence Wald considers himself a toolmaker. He is also an accomplished radiology professor at Harvard and an investigator at Massachusetts General Hospital.
In a recent presentation to the National Advisory Council for Biomedical Imaging and Bioengineering, Wald, a NIBIB grantee, explained how NIBIB fulfills an important role at NIH—supporting development of new tools and instrumentation, which is essential for scientific progress.
Examples he gave of the connection between development of new technologies and scientific breakthroughs included how Galileo’s telescope resulted in the end of the heliocentric theory of the universe and how the development of X-rays by William Roentgen resulted in widespread use of X-rays in the clinic in a mere 5 years. In each era, these toolmakers came to be known as the fathers of modern science in their respective disciplines.
Dr. Lawrence Wald of Harvard and MGH
Photo: Smita Jacob, MGH
Even though magnetic resonance imaging (MRI)–Wald’s field of study–has been used for more than 20 years now, he believes that we have just scratched the surface of harnessing MRI’s capabilities. Following the examples of Galileo and Roentgen, he is building new tools to dramatically expand the potential uses of MRI, a technology considered “miraculous” when first created.
He explained how several years ago, a 14-year-old girl with epilepsy was having 20 seizures per day. Using standard single-coil MRI, her brain appeared normal. However, a few years later when MRI systems incorporated additional coils, or detectors (4 coils instead of one) the images were higher resolution and revealed a malformation in the cortex, which was then removed surgically. The surgery rendered the patient seizure-free.
Epilepsy is just one example of how better images can transform diagnosis and treatment of neurological disorders that are described only by symptoms, because the physical causes are unknown. Improved imaging may reveal the underlying pathology and enable the appropriate therapy.
Many MRI advances have come from software that is developed to enhance images after the hardware captures the image. Devices with only one or a few detectors capture a fixed amount of information to create images. Increasing the number of detector coils several fold, so they form an array of coils that surround the subject, creates a higher resolution image by capturing more information during the procedure. The Wald lab is building such array-based devices that improve image clarity and speed up procedure times.
To obtain higher resolution MRI images, the group built a unit that surrounds the head with an array of 64 detector coils. An additional component, containing 19 detector coils, was built to image the area around the cervical spine (C-spine), which is difficult to do with conventional MRI detectors. Each coil provides an additional channel throughwhich image information is transmitted during the MRI.
The C-spine device was sensitive enough to obtain high resolution images of the cervical vertebrae in healthy control individuals as well as in those with amytrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. The 19-coil C-spine array, for the first time, revealed an image of the inflammation present in the spine of an ALS patient. The image exposed an underlying physical pathology associated with the disease, which had previously only been described by symptoms observed in individuals with ALS.
The MRI technology currently in use requires large, expensive magnets and tons of metal shielding; it also consumes a lot of energy and needs sophisticated cryogenics to cool the mammoth system. Such systems currently exist only in the radiology departments of large hospitals. Thus, another goal is to develop tools to create much smaller MRI devices that can be transported easily and used in a wide range of settings, including remote regions. These smaller, portable MRIs that Wald’s lab is building do not create the high-resolution images obtained with large, immobile MRI devices. However, the smaller devices with lower resolution still provide enough clarity to detect critical conditions that require rapid interventions.
These include conditions that involve the rapid accumulation of fluid in the brain such as edema in severe preeclampsia in pregnant women, which increases a woman’s risk of stroke and development of cardiovascular disease. Identification of the condition with MRI allows for monitoring and treatment to reduce the risk of future cardiovascular events. Another example is hydrocephalus, which can be congenital or resulting from head injury or infection. Approximately six of 10 people with hydrocephalus die without treatment. Identification of the condition with MRI allows for the immediate insertion of a shunt to drain the deadly buildup of cerebral spinal fluid.
“Our goal is to develop an MRI system with a magnet I can hold in one hand and the rest of the device I can hold in the other,” says Wald. “The device would have reduced sensitivity but would be good enough to give a ‘yes’ or ‘no’ answer at the point of care about whether a patient has a life-threatening injury or condition that requires immediate attention.”
The group has developed a prototype, which features the small, lightweight magnet Wald envisioned.
The lab plans to test the portable prototype in Uganda. Wald explains the significance of bringing their technology to the site in Africa: “Hydrocephalus is a life-threatening condition, common in developing countries where it is caused by infectious diseases. It is a situation where the swelling of the brain means certain death, but if diagnosed in time can be relieved by the relatively simple insertion of a shunt.”
Wald’s work to improve MRI receives high praise from NIBIB director Dr. Roderic Pettigrew. “Twenty-five years after the discovery of MRI, which, at the time was considered a phenomenal ground-breaking technology, Dr. Wald’s team is inventing new tools to revolutionize the use of MRI. It is an outstanding example of the technology development that NIBIB supports—innovative creation of game-changing breakthroughs with the potential to significantly improve and widen access to health care in the U.S. and worldwide.”