Developed at MIT a technique which combines several types of magnetic resonance imaging (MRI), could allow doctors to better monitor patients’ progression and track the effectiveness of potential new treatments. The study, published this week in the Archives of Neurology, is the first to provide clinical evidence for the theory that Parkinson’s neurodegeneration begins deep in the brain and advances upward.
Heiko Braak, an anatomist in Frankfurt, Germany, classified Parkinson’s disease into six stages, based on the appearances of the affected brain structures. In 2004, he proposed that during the earliest stages, a structure deep inside the brain, known as the substantia nigra, begins to degenerate. This structure is critical for movement and also plays important roles in reward and addiction. Later, Braak proposed, degeneration spreads outward to a brain region known as the basal forebrain. This area, located behind the eyes, includes several structures that produce acetylcholine, a neurotransmitter important for learning and memory. Post-mortem studies verified this sequence of events, but it had never been observed in living patients because the substantia nigra, deep within the brain, is so difficult to image with conventional MRI.
The MIT team used four types of MRI scans, each of which uses slightly different magnetic fields, generating different images. By combining these scans, the researchers created composite images of each patient’s brain that clearly show the substantia nigra and basal forebrain. The research team scanned 29 early-stage Parkinson’s patients and found significant loss of volume in the substantia nigra early on, followed by loss of basal forebrain volume later in the disease, as predicted by Braak. The findings appear to correlate with the appearance of symptoms in Parkinson’s patients and suggests that two different systems of the brain — one dopaminergic and associated with motor control, and one cholinergic and associated with cognitive function — have different timing.
This MRI technique demonstrates the potential to follow patients over time and measure whether degeneration of the two areas is correlated or if they deteriorate independently of one another. It could also give doctors a new way to monitor how their patients are responding to current and future treatments.