Dozens would scoff at the diagnosis.
But there it was — incontrovertible in the bright red and purple images of the organ and the glowing assessment of the physician interpreting them.
“You have a gorgeous brain,” said Dr. David Mikulis as he perused the magnetic resonance imaging scans of my noggin arrayed across his monitor.
“It’s beautiful,” the neuroradiologist added.
The pictures were produced during a half-hour session in the tubular MRI scanner, a top-drawer horror of immobilized claustrophobia and industrial-rock auditory assaults.
Adding to that unpleasantness, there was the intermittent feeling of breathlessness caused by the elevated carbon dioxide load being fed to the oxygen mask taped over my face.
But that extra CO2 — which upped my blood concentrations of the gas more than 20 per cent from those I produce through normal respiration — was the point of the entire MRI episode.
That’s because the brain’s natural reaction to higher CO2 levels is to widen the vessels feeding it, to allow more oxygen-carrying blood to flow through.
It’s the extent of that vascular expansion that Mikulis and his partner at Toronto Western Hospital, Dr. Joe Fisher, are seeking as they tune what they hope will prove a new standard test for a variety of neurological ailments.
In a field known as a cerebrovascular reactivity (CVR) measurement, Mikulis and Fisher are currently conducting early studies to determine how well their unique diagnostic procedure might work.
The two, who invited the Toronto Star to try it out, say their CVR testing could provide sentinel signs of stroke and other brain disorders, and even early warnings of Alzheimer’s disease.
These are “early, early days,” Fisher, an anesthesiologist, says of the CO2-based test. “It’s like discovering a microscope and putting everything under the microscope to see what’s there.”
The eventual goal of the research, however, is to win Health Canada and U.S. Food and Drug Administration approval for its use in a number of neurological applications.
The test works like this:
Brain vessels that widen as they should in reaction to increased CO2 levels allow a higher volume of blood to pass through. And it’s this increased blood flow that the MRI is detecting, revealing it in colour-coded images of hot purples and reds.
The vessels that don’t expand in the presence of CO2 — due to hardening diseases or other disorders — produce drabber, cooler images marked by blues and greys.
(Despite a decades-long absence by its owner of healthy personal tending, my brain decidedly tended towards the hotter spectrum of colours throughout.)
Other CVR measurement methods also use CO2 to examine vascular health in the brain. But the key to the Toronto Western test is a trademarked investigational device, known as a RespirAct and developed by Fisher, that can precisely control CO2 blood concentrations.
“With other methods that attempt to change blood carbon dioxide levels, the levels do change but the amount of change is unknown, so CVR measurement with these methods is imprecise,” Mikulis says.
“There is no attempt to regulate the flow of carbon dioxide, so the methods are very sloppy.”
The precise CO2 regulation achieved by Fisher’s device ensures the brain is being bathed with known and even amounts of the gas, Mikulis says.
“And since we know quantitatively what the carbon dioxide levels are, we can correlate that to the MRI images and actually create maps in the brain that show how each part … responds to the carbon dioxide stressor,” he adds.
“If you have a normal blood flow increase … that’s great. But some people with blood vessel disease don’t have an increase in blood flow, which they should have, so that tells us they have disease.”
Such vascular deficiencies in the brain are related to a host of serious neurological conditions and risks, notes Mikulis.
For example, he has a federal Canadian Institutes of Health Research grant to study the utility of his CVR procedure as a predictor of future Alzheimer’s disease.
“The idea behind Alzheimer’s disease is that it looks like the trigger for it could be deterioration in the brain blood vessels,” Mikulis says.
“That sets off a cascade of biochemical processes that then go on to increase the deposition of (Alzheimer’s disease-causing products) in the brain.”
In the research, Mikulis will be studying patients with mild cognitive impairment (MCI), indicated by memory loss, but who do not have full-blown Alzheimer’s. Some 15 per cent of MCI patients will go on to develop the more severe disease each year, he says.
“So we’re taking these MCI patients and scanning them using this (RespirAct) device, and then we’re taking patients with known Alzheimer’s disease and scanning them,” Mikulis says.
“And we will end up comparing the maps that we generate because what we think is we’ll begin to see in the MCI data the early changes in the maps that reflect what we actually end up seeing in true Alzheimer’s disease.”
In particular, the scans will be looking to map signature changes in areas of the brain most associated with the ailment — changes that are present before its devastating and irreversible neurological shrinkage occurs.
This search for early signs of Alzheimer’s — markers for the disease’s likely onset — can allow physicians to target high-risk patients with existing and emerging medications before they develop full-blown dementia.
At about $500 a pop, the Toronto Western test will likely prove far cheaper than other proposed scans, which involve radioactive tracers that cling to Alzheimer’s-causing amyloid proteins in the brain and cost between $3,000 and $4,000.
“As well, if you know who is going to get Alzheimer’s disease, you’re going to be using potentially expensive therapies to treat that,” Mikulis says.
“You don’t want to give (those costly therapies) to someone who is not going to get the disease.”
Fisher says a recent study that looked at a single brain artery showed that CVR status was also the single most important indicator of stroke risk.
“We not only know what’s happening in one artery, we know what’s happening in your whole brain in three dimensions,” he says.
“We have a very fine, millimetre-by-millimetre picture … over your whole brain, knowing where the areas are that are at risk.”
Mikulis and Fisher have performed their CVR testing — which maintains constant and normal oxygen flow to its subjects — on almost 1,000 patients and have shown it to be eminently safe.
“We’ve done it in patients who have severe, severe cerebral vascular disease, like some patients living on just one little artery supplying the entire brain,” says Mikulis. “And we’ve never had a complication.”
Indeed, Mikulis says, the CO2 levels they induce in their subjects, though sometimes disconcerting, are virtually the same as those produced during sleep, when respiration slows and the gas is exhaled less readily.
“Or if you held your breath for about 30 seconds, that’s what it would be like,” he says.
Now, if they could just quiet the electromagnetic clanging of an MRI machine.
Healthy and unhealthy brain with elevated CO2 levels
The above photo arrays show the magnetic resonance imaging scans of two brains as they react to increased carbon dioxide levels in the blood.
The set on the right represents different views of reporter Joseph Hall’s brain. The purple and red colours indicate healthy reaction of the organ’s blood vessels to the precisely controlled CO2 hikes, administered via a breathing mask while he was being scanned in the tubular machine. The dark colours show the higher blood flows that occur when the veins and arteries open up as they should as the gas spikes some 20 per cent above normal levels.
The left set of pictures portrays a brain with damaged or diseased vasculature. The blue areas in the images show regions where the vessels failed to open up wider as they were bathed with increased CO2. Brain segments that lack a healthy opening capacity — or cerebrovascular reactivity — are at far higher risk for stroke and other neurological ailments.