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...
The authors review the theoretical basis of determination of cerebral blood flow (CBF) using dynamic measurements of nondiffusible contrast agents, and demonstrate how parametric and nonparametric deconvolution techniques can be modified for the special requirements of CBF determination using dynamic MRI. Using Monte Carlo modeling, the use of simple, analytical residue models is shown to introduce large errors in flow estimates when actual, underlying vascular characteristics are not sufficiently described by the chosen function. The determination of the shape of the residue function on a regional basis is shown to be possible only at high signal-to-noise ratio. Comparison of several nonparametric deconvolution techniques showed that a nonparametric deconvolution technique (singular value decomposition) allows estimation of flow relatively independent of underlying vascular structure and volume even at low signal-to-noise ratio associated with pixel-by-pixel deconvolution.
The T1 perfusion model has worked well in brain functional studies where flow changes are measured. Using selective and nonselective inversion pulses, a new method has been developed to study steady-state brain blood flow. The authors obtained flow-sensitive images using selective inversion and flow-insensitive images using nonselective inversion. Subtraction of flow-insensitive images from flow-sensitive images gave us flow-weighted images with good gray-white flow contrast in cortical gray matter as well as in the thalamus and basal ganglia. Fitting T1s of flow-insensitive and flow-sensitive images allowed us to obtain preliminary results of brain blood flow maps. Two specific problems can seriously affect the accuracy of the brain blood flow values and the gray-white flow contrast of brain blood flow maps. These are the problems of the partial volume effect of CSF and gray matter, and the difference between blood T1 and white matter T1. The authors discuss in detail the character of these problems and present a number of approaches to manage such problems.
The goal of this work was to develop a comprehensive understanding of the relationship between vascular proton exchange rates and the accuracy and precision of tissue blood volume estimates using intravascular T1 contrast agents. Using computer simulations, the effects of vascular proton exchange and experimental pulse sequence parameters on measurement accuracy were quantified. T1 and signal measurements made in a rat model implanted with R3230 mammary adenocarcinoma tumors demonstrated that the theoretical findings are biologically relevant; data demonstrated that over-simplified exchange models may result in measures of tumor, muscle, and liver blood volume fractions that depend on experimental parameters such as the vascular contrast concentration. As a solution to the measurement of blood volume in tissues with exchange that is unknown, methods that minimize exchange rate dependence were examined. Simulations that estimated both the accuracy and precision of such methods indicated that both the inversion recovery and the transverse-spoiled gradient echo methods using a "no-exchange" model provide the best trade-off between accuracy and precision.
Measuring tissue blood flow with NMR imaging of intravascular tracers is more difficult than measurements of tissue blood volume. One major obstacle to the application of the Central Volume Principle is the direct measurement of the mean transit time. In this note, we demonstrate that mean transit time (MTT), which relates tissue blood volume to blood flow via the Central Volume Principle, is not the first moment of the concentration-time curve for MR or CT imaging of purely intravascular tracers. However, while first moment methods cannot be used by themselves to determine absolute flow, we show that transit curves may provide a useful relative measure of flow, for example, by considering ratios of the first moments.
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