Experimental estimates of the constants relating signal change to contrast concentration for cerebral blood volume by T2* MRI.

Estimates of cerebral blood volume (CBV) obtained from dynamic contrast T2(*)-weighted magnetic resonance imaging (MRI) tend to be significantly higher than values obtained by other methods. This may relate to the common assumption that the proportionality constants relating signal change to contrast concentration are equal in tissue and artery. To test this hypothesis and provide estimates for the ratio of those proportionality constants, the authors compared measurements of CBV by both MRI and computed tomography (CT) scans in nine healthy volunteers obtained using identical kinetic paradigms for the two imaging modalities. Both boluses and infusions of contrast were studied. Measurements were made in nine anatomic regions of interest of the cerebral hemispheres bilaterally. Cerebral blood volume values obtained by CT were generally lower than those obtained by MRI, especially in the cerebral cortex. As a result, the calculated values of the ratios of proportionality constants relating signal change to concentration in tissue and artery after bolus injections were significantly less than 1 in cortex (0.69) and white matter (0.76), although not in deep gray matter structures (0.87). Values of the ratios based on infusion measurements were closer to 1. In addition, CBV measurement errors with bolus MRI were significantly larger than those observed with infusion MRI or by CT. The reasons that the constants differ from 1 and for the larger variance of bolus MRI are discussed in terms of the T2* signal mechanisms. These studies help define the magnitude by which CBV is overestimated with typical T2*-weighted perfusion imaging. Infusion measurements of CBV can reduce the variance intrinsic to T2* MRI and lessen the likelihood of type II error.

Cerebral blood volume measurements by rapid contrast infusion and T2*-weighted echo planar MRI.

Cerebral blood volume (CBV) provides information complementary to that of cerebral blood flow in cerebral ischemia, tumors, and other conditions. We have developed an alternative theory and method for measuring CBV based on dynamic imaging by MRI or CT during a short contrast infusion. This method avoids several limitations of traditional approaches that involve waiting for steady state or measuring the area under the curve (AUC) during bolus contrast injection. Anesthetized dogs were studied by T2*-weighted echo planar imaging during gadolinium-DTPA infusions lasting 30-60 sec. CBV was calculated from the ratio of the signal changes in tissue and artery. Method responsiveness was compared to AUC measurements using the vasodilator acepromazine. The ratio of signal change in tissue to that in artery rapidly approached an asymptotic value even while the amount of contrast in artery continued to increase. Using 30-sec infusions, the mean (+/- SD) of CBV for control animals was 3.6 +/- 0.9 ml blood/100 g tissue in gray matter and 2.3 +/- 0.8 ml blood/100 g tissue in white matter (ratio = 1.6). Acepromazine increased CBV to 5.7 +/- 1.5 ml blood/100 g tissue in gray matter and 3.1 +/- 0.8 ml blood/100 g tissue in white matter (ratio = 2.0). AUC measurements after bolus injection yielded similar values for control animals but failed to demonstrate any change after acepromazine. It is possible to measure CBV using dynamic MRI or CT during 30-60-sec contrast infusions. This method may be more sensitive to changes in CBV than traditional AUC methods.

Calcium compartments in brain.

Excellent progress has been made toward understanding the physiology and pharmacology of specific calcium-related cellular processes of the brain, but few studies have provided an integrated view of brain calcium kinetics. To further the knowledge of the size and binding properties of brain calcium compartments, the authors have conducted a series of experiments in hippocampal brain slices exposed to high and low extracellular calcium. Slices were incubated in buffers containing 0.001 to 4.5 mmol/L calcium for up to 75 minutes. Slice calcium content was analyzed by three methods: exchange equilibrium with 45Ca, synchrotron-radiation-induced x-ray emission, and inductively coupled plasma. Data were analyzed using a model based on a Langmuir isotherm for two independent sites, with additional extracellular and bound compartments. In parallel experiments, altered low calcium had no effect on slice histology and only mild effects on slice adenylates. When combined with prior 45Ca and fluorescent probe binding experiments, these results suggest that there are at least five kinetically distinct calcium compartments: (1) free extracellular (approximately 10%); (2) loosely associated extracellular plasma membrane (approximately 55%); (3) intracellular compartment with moderate avidity (approximately 17%); (4) tightly bound, nonexchangeable intracellular compartment ( approximately 15%); and (5) free cytoplasmic (<0.01%). If only the third compartment is considered a potential calcium buffer, then the buffering ratio is calculated to be approximately 2,700:1, but if the second compartment is also included, then the buffering ratio would be approximately 13,000:1. This may explain the wide range of estimates observed by fluorescent probe studies.