Breakthrough: Unmasking Early-Stage Alzheimer's Disease
Reducing MRI Analysis Time from 100 Hours to Less than 10 Minutes

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“Debbie, have you seen my keys?”

We all ask questions like that. In an active life, it’s easy to lose track of things when we’re distracted, in a hurry, or in multi-tasking overload.

But mild forgetfulness, when it appears to be progressive, can have a different meaning for people in their 60s, 70s, or 80s. It may stem from a variety of causes, including stress; but it can also be an early indicator of Alzheimer's disease (AD) or less common neurological problems. This sums up the challenge facing neurologists when they see a patient with what is known as mild cognitive impairment (MCI). How can they diagnose AD with a high degree of certainty in the early stages – when it may still be possible to arrest it?

Professor James Brewer of the University of California at San Diego (UCSD) is doing groundbreaking work with a Mac-based diagnostic system known as NeuroQuant that automates analysis of magnetic resonance (MRI) images of the brain. He is the first physician to use this technology on a clinical basis to examine patients’ brains for the tell-tale effects of Alzheimer's disease.

“Diagnosing Alzheimer’s may be helped by taking volume measurements of regions of the brain,” says Brewer. “The old way of doing this is unbelievably painstaking. The MRI is 256 slices with 256x256 resolution, so every voxel is about a millimeter in each direction. One used to have to flip through the MRI slice by slice and trace the hippocampi and other brain regions on each slice using a program called Amira. That could take even an expert neuroanatomist 100 hours.

”Now I have a beautiful setup. The iMac sits on my desk and runs NeuroQuant, which processes an MRI and delivers a quantitative analysis of the entire brain structure in less than 10 minutes. This is a simple, powerful arrangement for doing both research and clinical practice.”

Brewer’s work will be of intense interest to clinical neurologists – and to anyone whose loved one is facing memory loss.

The Tragedy of Patient HM: Life without Memory

The mystery behind memory loss in AD began to unravel in Boston’s Hartford Hospital in 1957. A man known today as Patient HM came to the hospital suffering from severe epilepsy. He was 27 and unemployable, incapacitated by up to 11 seizures a day. Electroencephalography revealed that the source of the seizures was Patient HM’s hippocampi – a pair of seahorse-shaped organs not far from the inner ear. (“Put a fingertip in your ear,” says Brewer, “and it will be about an inch and a half from a hippocampus.”)

The hospital offered Patient HM an experimental procedure with no guarantee of success: removal of part of his medial temporal lobes, including his hippocampi. Patient HM agreed, and the procedure worked. From that point on his seizures were reduced to about two a year. But there was an extraordinary side effect: from that day forward he formed no new memories of any event. He could acquire knowledge and skills, and his pre-operation memories were intact, but nothing that happened afterwards remained in his memory, including the death of his mother and the first moon landing. He described his condition as constantly waking up from a dream and wondering where he was. Word of his plight inspired production of the acclaimed 2000 movie Memento, which Brewer says portrayed the symptoms accurately. The hero was forced to tattoo himself to retain vital information.

Once it became clear that the hippocampi are the gateways of episodic memory -- the memory of events – scientists were able to focus on them as the probable site of AD. Studies revealed that while the brain of a healthy person shrinks by nearly one percent per year, the hippocampi of an Alzheimer's patient shrinks at five times that rate.

“We’ve known since the early 90s that the hippocampus starts shrinking very early in the development of Alzheimer's disease,” says Brewer. “There are variants of the disease, but they’re very atypical.”

Today, with an aging US population and an increasing number of dementia patients, there’s a pressing need to apply this knowledge to clinical diagnosis. But neurologists have been severely technology-limited. What they need is a practical, quantified way to compare their patients’ hippocampi with the hippocampi of healthy people of the same age. MRI scans can deliver high-resolution DICOM-format image slices of a patient’s brain. But to manually quantify 256 hippocampi MRI image slices is, as Brewer points out, a mind-numbing, weeks-long job – an impossibility for routine diagnosis.

NeuroQuant: Automated, Mac-Based MRI Analysis

When NeuroQuant receives a set of DICOM images, it checks image quality and automatically segments (assembles) the image slices into a single 3D volume image. It then electronically isolates the brain from the skull and its membranes, segregates grey matter from white (connective nerve tissue), identifies and quantifies all regions of the brain with great accuracy, and delivers a statistical report including colorized images – all in about 8.5 minutes of processing on Brewer’s iMac.