Physicians have sought useful images of the brain almost since the discovery of x-rays, but for decades, little useful information could be obtained. The great breakthrough occurred in the past 20 years as imaging became able to depict chemistry, not just structure. Today, brain imaging is crucial to the treatment of some of the most serious diseases and is adding to knowledge of how the brain functions and malfunctions.
Two of the most serious disorders affecting the brain are cerebrovascular accident (CVA) and ruptured aneurysm. CVAs occur in the United States at the rate of one every 40 seconds. About two thirds of CVA patients survive, but as many as 40% of them are left with significant disability. It is to reduce this burden that thrombolytic techniques have been developed, public education has been provided, and specialty CVA centers have been established. If thrombolysis is to be effective, however, the correct diagnosis of occlusive or hemorrhagic CVA must be made quickly; prompt, high-resolution imaging is mandatory.
On Nov. 14, at the 2000 meeting of the American Heart Association, Gregory Albers, MD, director of the Stroke Center at Stanford University, Stanford, Calif, outlined in his presentation “Stroke in the New Millenium” the capabilities of the gold standard for CVA imaging: diffusion-perfusion MRI. On diffusion-weighted imaging, an area of CVA is bright white, enabling the neurology team to determine its location and size easily. These images also make it possible to detect the small emboli that suggest the heart or aorta as the source of the CVA. In almost half of a series of patients in an ongoing study at Stanford, diffusion-weighted imaging provided more information than did standard MRI or CT. When perfusion-weighted imaging is added, it is possible to assess the patient’s prognosis and suitability for thrombolytic therapy.
On April 16, 2001, at the 26th International Stroke Conference, Fort Lauderdale, Fla, Chelsea S. Kidwell, MD, associate director of the UCLA Stroke Center, described a model for predicting transformation of an infarcted area to a hemorrhagic one, a dreaded complication of thrombolytic therapy. In an analysis incorporating the volume and severity of changes in the apparent diffusion coefficient, the risk of hemorrhagic transformation in a given patient could be predicted with 95% accuracy. Thus, thrombolytic infusion could be reduced or stopped. Kidwell warned clinicians that the method requires validation. The UCLA team also has employed diffusion-weighted imaging and perfusion-weighted imaging to prove that infarct-induced damage to the brain can be reversed using intra-arterial thrombolysis,1 sometimes as late as 6 hours after the onset of symptoms. It may eventually be possible to determine the thrombolysis treatment window using an MRI-measured physiologic clock instead of? a time clock.
Ultrasonography also is finding a place in CVA imaging. James C. Grotta, MD, professor and Huffington chair of neurology, University of Texas Medical Center, Houston, has described the utility of transcranial Doppler ultrasonography in studying blood flow inside the brain. In Grotta’s view, intravenous thrombolysis monitored ultrasonographically could prove to be as successful as the more costly intra-arterial thrombolysis with MRI monitoring.
Michael H. Lev, MD, director of emergency neuroradiology at Massachusetts General Hospital, Boston, noted that contrast-enhanced CT angiography (CTA) is “ready for prime time,” during a presentation at the April 2000 meeting of the American Society of Neuroradiology. Lev et al described a protocol incorporating standard CT scanning, CTA, and perfusion studies. The combination provided a clear picture of the penumbra (the damaged tissue that might be salvaged using thrombolysis). In most patients, suitability for thrombolytic therapy could be determined before the patient left the scanner.
CTA may also have an important role in evaluating intracranial aneurysms. In a study by Villablanca et al,2 volume-rendered helical CTA proved to be “better, safer, faster, and cheaper” at obtaining images of these lesions.
Recent insights into the chemical changes of Alzheimer disease have led to the rational development of drug candidates that may inhibit or reverse these devastating abnormalities. Thus, it has become vital to be able to distinguish this type of dementia from the many other types that affect humans. Both MRI and positron-emission tomography (PET) have been called on for diagnosis. Both modalities also show promise in predicting which high-risk patients will eventually have Alzheimer disease.
In April 2001, investigators from the Dementia Research Group at the Institute of Neurology, London, demonstrated that volumeric volumetric MRI can differentiate semantic dementia from Alzheimer disease.3 Patients with semantic dementia, which prevents victims from correlating images or words with their meanings, had left-sided temporal lobe atrophy, particularly in the front. In patients with probable Alzheimer disease, however, the atrophy was equal bilaterally and showed no predilection for the front of the temporal lobes. Ronald C. Peterson, MD, PhD, of the department of neurology, Mayo Clinic, Rochester, Minn, wrote an editorial accompanying the research report. He believes that the findings could be valuable to clinicians in counseling patients and families. Alzheimer’s disease and some other dementias have known but different inheritance patterns, which “can have huge implications for families,” he notes.
A functional MRI (fMRI) study by Susan Y. Bookheimer, MD, and her colleagues of the department of psychiatry and behavioral sciences, University of California Los Angeles, suggests that the brain tries to compensate for the early changes of Alzheimer disease by firing more neurons.4 These investigators scanned subjects who were cognitively normal while they were recalling unrelated pairs of previously memorized words. Half of the patients were carriers of a gene that predisposes them to Alzheimer disease. They demonstrated greater activation in the areas affected by Alzheimer disease than did the other subjects. Those participants showing the greatest degree of activation were most likely to demonstrate memory loss when re-examined 2 years later.
MR spectroscopy also shows promise. Kantarci et al5 studied a series of elderly patients without cognitive impairment, with probable Alzheimer disease, and mild cognitive impairments considered transitional between normal aging and Alzheimer disease. The earliest change seen was an increase in the ratio of myoinositol (a product of inflammation) to creatine. Clifford R. Jack, Jr, MD, professor of radiology and one of the investigators in this study, noted that MR spectroscopy in combination with a structural MRI scan to measure brain atrophy might make it possible to determine the likelihood that an at-risk person will develop Alzheimer disease at a cost of approximately $400.
Despite these good results with MRI, the chief imaging study used for Alzheimer disease is PET. Reduced metabolism in the temporal and parietal lobes, seen bilaterally, is characteristic. In a study6 that involved 22 patients with memory loss or dementia who eventually underwent autopsy, bilateral temporoparietal hypometabolism, as detected by PET with fluorodeoxyglucose, exhibited 93% sensitivity, 63% specificity, and 82% accuracy in identifying Alzheimer disease. Thus, if PET does not show this pattern of hypometabolism in a demented patient, the investigators recommend suspecting a disorder other than Alzheimer disease. In almost one fourth of the patients enrolled in this study, the diagnosis of Alzheimer disease most assuredly would have been missed in the absence of the PET findings.
Two groups of investigators have attempted to use PET to identify patients who will later develop Alzheimer disease, along with those who are in the earliest stages of the disease. Jelic and Nordberg7 suggest that mild forms of the metabolic abnormalities that are characteristic of Alzheimer disease can be detected using PET in persons who do not yet have signs and symptoms. Another team8 studied elderly patients over time using structural MRI. The characteristics of three areas of the brain-the entorhinal complex cortex the superior temporal sulcus, and the anterior cingulate gyrus-always correctly distinguished normal subjects from those with Alzheimer disease. It also was possible to predict which patients with cognitive decline would not later develop Alzheimer disease with 85% accuracy.
At some medical centers, MRI scanners are standard equipment for brain tumor surgery. The essential problem faced by the neurosurgeons is that brain tumors cannot typically be identified by surgeons who are simply looking at them. Moreover, when cerebrospinal fluid is drained off, the brain shrinks, and as the tumor is resected, the brain tissue flows into the defect; preoperative maps of the tumor are no longer accurate.
Surgeons also use fMRI preoperatively to delineate critical areas of the brain where they should not cut. To its practitioners, intraoperative MRI is an important surgical tool that is used in much the same way that an operative microscope is used.
William G. Bradley, MD, PhD, director of MRI and medical research at Memorial Medical Center, Long Beach, Calif, is convinced that it will someday be considered malpractice to fail to use MRI when operating on low-grade gliomas; a minute portion of tumor that is not removed can transform itself into a highly malignant glioblastoma multiforme. In the first year of an unpublished study currently underway at his institution, MRI showed that some amount of tumor had been left behind in 80% of the cases in which the surgeon felt that the resection had been complete. The following year, the use of intraoperative MRI by the surgeons increased dramatically.
Many approaches to brain imaging are finding a place in clinical practice, especially for intraoperative guidance, dementia diagnosis, and CVA characterization. The implications of brain imaging on the understanding of normal and abnormal mental processes will be profound.
NOTE: References can be accessed in the online version of this article at www.imagingeconomics.com.
Judith Gunn Bronson is a contributing writer for Decisions in Axis Imaging News.
- Kidwell CS, Saver JL, Mattiello J, et al. Thrombolytic reversal of acute human cerebral ischemic injury shown by diffusion/perfusion magnetic resonance imaging. Ann Neurol. 2000;47:462-469.
- Villablanca JP, Martin N, Jahan R, et al. Volume-rendered helical computerized tomography angiography in detection and characterization of intracranial aneurysms. J Neurosurg. 2000; 93:254-264.
- Chan D, Fox NC, Scahill RI, et al. Patterns of temporal lobe atrophy in semantic dementia and Alzheimer?s disease. Ann Neurol. 2001;49:433-442.
- Bookheimer SY, Strojwas MH, Cohen MS, et al. Patterns of brain activation in people at risk for Alzheimer?s disease. N Engl J Med. 2000;343:450-456.
- Kantarci K, Jack CR Jr, Xu YC, et al. Regional metabolic patterns in mild cognitive impairment and Alzheimer?s disease: a 1H MRS study. Neurology. 2000;55:210-217.
- Hoffman JM, Welsh-Bohmer KA, Hanson M, et al. FDG PET imaging in patients with pathologically verified dementia. J Nucl Med. 2000;41:1920-1928.
- Jelic V, Nordberg A. Early diagnosis of Alzheimer disease with positron emission tomography. Alzheimer Dis Assoc Disord. 2000;14:S109-S113.
- Killiany RJ, Gomez-Isla T, Moss M, et al. Use of structural magnetic imaging to predict who will get Alzheimer?s disease. Ann Neurol. 2000;47:430-439.