Functional Magnetic Resonance Imaging

A number of functional MRI techniques have recently been developed that can also measure cerebral perfusion. Several studies have been performed with dynamic susceptibility contrast MRI (DSCMRI) in patients with AD. The principle behind this technique is that passage of a concentrated bolus of a paramagnetic contrast agent distorts the local magnetic field sufficiently to cause a transient loss of MR signal on pulse sequences designed to be maximally susceptible to magnetic field inhomogeneities, for example, a T2*-weighted sequence (74). The passage of contrast is imaged over time by sequential rapid scanning of the same slice. The rate of change of signal intensity over time can be calculated and gives a measure that has been shown in animal studies to be directly proportional to cerebral blood volume (CBV).

Gonzalez and collaborators (75) studied 10 patients with various types of dementia, including 5 with probable AD, with both PET and DSCMRI. They found a significant correlation between the modalities both quantitatively and qualitatively. Similarly, Johnson and colleagues (76) found CBV, as measured by DSCMRI, to correlate well with perfusion by SPECT in 16 patients with AD and 10 age-matched controls. Harris and colleagues (77) performed DSCMRI in 13 patients with AD and 13 controls, and found significantly reduced ratios of temporoparietal CBV to cerebellar CBV in the AD group. Three patients with very mild dementia (mean MMSE = 25.0) also had showed reductions in temporoparietal CBVs. Overall, they found that MMSE scores did not correlate well with temporoparietal CBV ratios.

Sandson and colleagues (21) performed noninvasive perfusion MRI with the echo-planar imaging and signal targeting with alternation radiofrequency (EPISTAR) technique (78) in 11 patients with AD and 8 age- and education-matched controls. The principle of EPISTAR is based on the acquisition of a pair of images, in one of which arterial blood outside of the imaging slice has been magnetically labeled by applying a 180-degree inversion radiofrequency pulse to the protons in the arterial water. Focal areas of hypoperfusion were

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Fig. 3. Axial images from a 53-year old man with biopsy-proven Alzheimer's disease. (Left) Structural MRI (Tl-weighted). (Center) EPISTAR perfusion weighted MRI demonstrating bilateral posterior temporal-occipital perfusion deficits, (Right) 99Tc-HMPAO SPECT image demonstrating similar perfusion deficit at same slice plane.

seen in the posterior temporoparietal-occipital region in seven of the patients with AD (Fig. 3). Parietooccipital and temporooccipital to whole-slice signal intensity ratios were significantly lower in the AD patients, and parietooccipital ratios did correlate with dementia severity as measured by the Blessed Dementia Scale-Information-Memory-Concentration subtest (30).

The sensitivity and specificity of the fMRI techniques reported in these preliminary studies are comparable to those reported for PET and SPECT (6,46,79). One advantage of the fMRI techniques over other functional neu-roimaging modalities is that the MR structural imaging study can be performed during the same scanning session with the same scan plane, image size (field-of-view), and slice thickness as the functional MR scan. Specific regions of interest (ROI) can therefore be selected with a high degree of certainty on the structural image and directly transferred to the perfusion image at the same anatomical site. Furthermore, there is no exposure to ionizing radiation. EPISTAR offers the advantage of being completely noninvasive. DSCMRI is available as a multislice sequence, while multiple slices can only be acquired sequentially with EPISTAR. Quantification of cerebral blood flow is possible with both DSCMRI and EPISTAR (80,81).

Activational studies with fMRI in Alzheimer's disease are currently ongoing (82,83). These studies utilize another T2*-weighted technique called BOLD (84), which uses changes in the level of oxygenated hemoglobin in capillary beds to visualize areas of regional brain "activation." These preliminary reports have found decreased fMRI activation in hippocampal and pre-frontal regions in patients with AD compared with older control subjects (82,83).

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