Neuronal activity causes local changes in cerebral blood flow, blood volume, and blood oxygenation. Magnetic resonance imaging (MRI) techniques sensitive to changes in cerebral blood flow and blood oxygenation were developed by high-speed echo planar imaging. These techniques were used to obtain completely noninvasive tomographic maps of human brain activity, by using visual and motor stimulus paradigms. Changes in blood oxygenation were detected by using a gradient echo (GE) imaging sequence sensitive to the paramagnetic state of deoxygenated hemoglobin. Blood flow changes were evaluated by a spin-echo inversion recovery (IR), tissue relaxation parameter Tl-sensitive pulse sequence. A series of images were acquired continuously with the same imaging pulse sequence (either GE or IR) during task activation. Cine display of subtraction images (activated minus baseline) directly demonstrates activity-induced changes in brain MR signal observed at a temporal resolution of seconds. During 8-Hz patterned-flash photic stimulation, a significant increase in signal intensity (paired t test; P < 0.001) of 1.8% ± 0.8% (GE) and 1.8% ± 0.9% (ID) was observed in the primary visual cortex (Vi) of seven normal volunteers. The mean rise-time constant of the signal change was 4.4 ± 2.2 s for the GE images and 8.9 ± 2.8 s for the IR images. The stimulation frequency dependence of visual activation agrees with previous positron emission tomography observations, with the largest MR signal response occurring at 8 Hz. Similar signal changes were observed within the human primary motor cortex (Ml) during a hand squeezing task and in animal models of increased blood flow by hypercapnia. By using intrinsic blood-tissue contrast, functional MRI opens a spatialtemporal window onto individual brain physiology. The brain possesses anatomically distinct processing regions. A complete understanding of brain function requires determination ofwhere these sites are located, what operations are performed, and how distributed processing is organized (1). Changes in neuronal activity are accompanied by focal changes in cerebral blood flow (CBF) (2), blood volume (CBV) (3,4), blood oxygenation (3,5), and metabolism (6, 7). These physiological changes can be used to produce functional maps of component mental operations.Conventional magnetic resonance imaging (MRI) examinations provide high spatial-resolution anatomic images primarily based on contrast derived from the tissue-relaxation parameters T1 and T2. Recently, several investigators have demonstrated in animals that brain tissue relaxation is influenced by the oxygenation state of hemoglobin (a T* effect, modulated by the local blood volume) (8-13) and intrinsic tissue perfusion (T1 effect) (14)(15)(16). High-speed MRI techniques sensitive to these relaxation phenomena can thus be used to generate tomographic images of brain activity (17).We report here completely noninvasive MRI of brain activity by techniques with intrinsic sensitivity to CBF and blood oxygenation state. Time-resolved...
An echo planar linewidth mapping technique, Shufflebutt, has allowed temporal measurements of changes in linewidth caused by static inhomogeneities (delta LWSI) and transverse relaxation rate (delta R2) in models of hypoxia and hypercapnia. We demonstrate these changes are due to intravascular susceptibility differences/(delta chi) between the blood and tissue. Contrast agent injections at a delta chi equivalent to that of deoxygenated blood showed a twofold difference between the contrast agent and physiological anoxia values. Hypercapnia decreased both delta LWSI and delta R2 consistent with an increase in blood oxygenation. We attribute these findings to constant oxygen extraction during an increase in blood flow, resulting in less deoxygenated venous blood and thus reduced delta chi. For in vivo perturbations we found that delta R2/delta R2' approximately 0.33, a ratio much different from that measured in whole blood phantoms (delta R2/delta R2' approximately 2). This demonstrates that signal changes in these studies are produced predominantly by dephasing of extravascular protons due to field inhomogeneities produced by intravascular deoxygenated hemoglobin (deoxyHb).
To evaluate extent of bone marrow involvement and disease severity in Gaucher patients, results of modified Dixon quantitative chemical shift imaging (QCSI) of the lumbar spine were correlated with quantitative analysis of marrow triglycerides and glucocerebrosides and with quantitative determination of splenic volume at magnetic resonance (MR) imaging. High-field-strength MR spectra of surgical marrow specimens were dominated by a single fat and a water peak, validating use of QCSI. QCSI showed average vertebral marrow fat fractions of 10% +/- 8 in Gaucher patients (normal adult averages, 29% +/- 6). Relaxation times for lipid and water approximated normal averages; bulk T1 values were significantly longer, reflecting decreased marrow fat. Glucocerebroside concentrations were higher in Gaucher marrow and inversely correlated with triglyceride concentrations. Extent of marrow infiltration determined by fat fraction measurements correlated with disease severity measured by splenic enlargement. These results show that as Gaucher cells infiltrate bone marrow and displace normal marrow adipocytes, bulk T1 increases due to the higher T1 of water compared with that of fat. QCSI provides a sensitive, noninvasive technique for evaluating bone marrow involvement in Gaucher disease.
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