Nerve-cell death plays a key role in all neurodegenerative disorders. However, it has not previously been possible to study such events dynamically and in real time. Now, a research team headed up at University College London (UCL) in the UK has developed a simple, inexpensive eye test that can do just that. According to the researchers, imaging neuronal loss could prove invaluable in the early detection of disorders such as Alzheimer's disease (Cell Death and Disease 1 e3).
The test employs multiple fluorescent cell-death markers, which attach to nerve cells in the eye and indicate the phase of cell death. The retina is observed with a customized laser ophthalmoscope, enabling real-time imaging of retinal nerve cell death, and therefore brain cell death. Previously only used in vitro, the researchers have now demonstrated the scheme in an animal model, and plan to conduct the first patient trials later this year.
"This technique means we should be able to directly observe retinal nerve cell death in patients, which has a number of advantages in terms of effective diagnosis," explained Francesca Cordeiro of UCL's Institute of Ophthalmology. "This could be critically important since identification of the early stages could lead to successful reversal of the disease progression with treatment."
In addition to diagnosing and monitoring disease, the potential of this method to track changes in cell viability in vivo over several weeks could prove valuable for developing and assessing the efficacy of new therapeutic interventions. "Currently, the biggest obstacle to research into new treatments for neurodegenerative diseases is the lack of a technique where the brain's response to treatment can be directly assessed," said Cordeiro. "This technique could potentially help overcome that."
MR measurements
An Italian research team, meanwhile, is investigating the use of diffusion tensor imaging (DTI) to detect whether a person with memory loss has brain changes associated with Alzheimer's disease. DTI, an MR technique that measures the diffusion of water molecules within tissue, is more sensitive than traditional MRI for detecting changes in brain chemistry and can map the fibre tracts that connect brain regions (Neurology 74 194).
For the study, 76 healthy individuals aged 20 to 80 years underwent 3T MRI and diffusion-weighted brain scanning. The researchers examined DTI changes in the hippocampus, a region of the brain that's critical to memory and which is involved in Alzheimer's disease. Participants also performed perception tests to assess their verbal and visuospatial memory.
Scan results revealed that mean diffusivity in the hippocampus, measured via DTI imaging, predicted memory performance better than traditional MRI measurements of hippocampus volume, particularly in subjects aged 50 years or older.
"Our findings show this type of brain scan appears to be a better way to measure how healthy the brain is in people who are experiencing memory loss. This might help doctors when trying to differentiate between normal aging and diseases like Alzheimer's," said study author Giovanni Carlesimo, from Tor Vergata University in Rome. "DTI, along with MRI, could serve as an important tool in understanding how and why a person experiences memory decline."
PET progress
Elsewhere, researchers at the Feinstein Institute for Medical Research (Manhasset, NY) are employing PET to accurately differentiate Parkinsonian disorders. The various forms of Parkinsonism can present similar symptoms, but have different prognoses and respond differently to treatments. Early diagnosis is thus vital to ensure patients receive the correct treatment. It could also help enrol suitable subjects into trials of neuroprotective and disease-modifying drugs (Lancet Neurol. 9 149).
18F-fluorodeoxyglucose PET brain scans were performed on 167 patients with different forms of Parkinsonism, but uncertain clinical diagnosis. The researchers developed an automated image-based classification procedure to differentiate those with idiopathic Parkinson's disease, multiple system atrophy and progressive supranuclear palsy.
After imaging, the patients were assessed by movement disorders specialists for a mean of 2.6 years. The initial image-based classifications were then compared with the experts' final clinical diagnoses.
Image-based classification for idiopathic Parkinson's disease had 84% sensitivity, 97% specificity, 98% positive predictive value (PPV) and 82% negative predictive value (NPV). Imaging classifications were also accurate for multiple system atrophy (85% sensitivity; 96% specificity; 97% PPV; 83% NPV) and progressive supranuclear palsy (88% sensitivity; 94% specificity; 91% PPV; 92% NPV).
"The excellent specificity and PPV of the imaging classification makes this test suitable for diagnostic use rather than as a screening tool," said lead author David Eidelberg. The authors suggest that blinded, prospective imaging studies – ideally involving multiple centres, a larger validation group, repeat imaging and more extensive post-mortem confirmation – are needed to establish the accuracy of this pattern-based categorization procedure.