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The effect of hypercapnia on the cerebral metabolic rate of oxygen consumption (CMRO2) remains incompletely understood. This study examined the relationship between susceptibility (blood oxygenation level dependent (BOLD)) and perfusion-weighted (flow-sensitive alternating inversion recovery (FAIR)) MRI techniques both during induction of repeated transient hypercapnia (THC) and after return to normocapnia during whisker barrel functional activation. During induction of THC the FAIR signal became significantly elevated over control after 100 s of hypercapnia (P = 0.039), with a trend of increasing significance to 5 min (P = 0.000008). The FAIR signal in the activated cortex during subsequent normocapnia was significantly increased compared to pre-THC control after each successive period of THC. The mean grouped FAIR signal increased by 81% ± 63% after one exposure (P = 0.021), by 163% ± 55% after the second exposure (P = 0.0002), and by 240% ± 54% after the third exposure (P = 0.000002). The mean grouped BOLD signal trended upward, but did not increase significantly during or after exposure 1, 2, or 3. These data demonstrate increased uncoupling of perfusion-weighted from susceptibility imaging techniques, both in nonactivated cortex during hypercapnia, and with activation after multiple exposures to THC. These results are consistent with saturation of BOLD contrast as well as with increases in CMRO2 with stimulation after multiple exposures to THC. Magn Reson Med 48:262–270, 2002. © 2002 Wiley-Liss, Inc.

The effect of hypercapnia on the cerebral metabolic rate of oxygen consumption (CMRO2) remains incompletely understood. This study examined the relationship between susceptibility (blood oxygenation level dependent (BOLD)) and perfusion-weighted (flow-sensitive alternating inversion recovery (FAIR)) MRI techniques both during induction of repeated transient hypercapnia (THC) and after return to normocapnia during whisker barrel functional activation. During induction of THC the FAIR signal became significantly elevated over control after 100 s of hypercapnia (P = 0.039), with a trend of increasing significance to 5 min (P = 0.000008). The FAIR signal in the activated cortex during subsequent normocapnia was significantly increased compared to pre-THC control after each successive period of THC. The mean grouped FAIR signal increased by 81% ± 63% after one exposure (P = 0.021), by 163% ± 55% after the second exposure (P = 0.0002), and by 240% ± 54% after the third exposure (P = 0.000002). The mean grouped BOLD signal trended upward, but did not increase significantly during or after exposure 1, 2, or 3. These data demonstrate increased uncoupling of perfusion-weighted from susceptibility imaging techniques, both in nonactivated cortex during hypercapnia, and with activation after multiple exposures to THC. These results are consistent with saturation of BOLD contrast as well as with increases in CMRO2 with stimulation after multiple exposures to THC. Magn Reson Med 48:262–270, 2002. © 2002 Wiley-Liss, Inc.

The effect of hypercapnia on the cerebral metabolic rate of oxygen consumption (CMRO2) remains incompletely understood. This study examined the relationship between susceptibility (blood oxygenation level dependent (BOLD)) and perfusion‐weighted (flow‐sensitive alternating inversion recovery (FAIR)) MRI techniques both during induction of repeated transient hypercapnia (THC) and after return to normocapnia during whisker barrel functional activation. During induction of THC the FAIR signal became significantly elevated over control after 100 s of hypercapnia (P =0.039), with a trend of increasing significance to 5 min (P =0.000008). The FAIR signal in the activated cortex during subsequent normocapnia was significantly increased compared to pre‐THC control after each successive period of THC. The mean grouped FAIR signal increased by 81% ± 63% after one exposure (P =0.021), by 163% ± 55% after the second exposure (P =0.0002), and by 240% ± 54% after the third exposure (P =0.000002). The mean grouped BOLD signal trended upward, but did not increase significantly during or after exposure 1, 2, or 3. These data demonstrate increased uncoupling of perfusion‐weighted from susceptibility imaging techniques, both in nonactivated cortex during hypercapnia, and with activation after multiple exposures to THC. These results are consistent with saturation of BOLD contrast as well as with increases in CMRO2with stimulation after multiple exposures to THC. Magn Reson Med 48:262–270, 2002. © 2002 Wiley‐Liss, Inc.

An NMR method is applied for separating blood volume and magnetic susceptibility effects in response to neuronal stimulation in a rat model. The method uses high susceptibility contrast agents to enhance blood volume induced signal changes. In the absence of exogenous agent, the dominant source of signal change on neuronal activation is associated with the signal increase from the blood oxygen level dependent (BOLD) effect. The relative negative contribution of blood volume changes to BOLD changes is maximally estimated to be 34%. The blood volume changes associated with median nerve stimulation (7 Hz) in the motor cortex are 26 ± 7% and the corresponding blood susceptibility changes are 0.021 ± 0.006 ppm. These methods can be applied to enhance the sensitivity of fMRl signal response and provide accurate quantitative measures of blood volume response to stimulation.

An animal model of sensory activation using fMRI at 2.0 T has been developed, demonstrating that fMRI studies on animals need not be limited to high field magnets. These methods produced reliable image intensity changes of 2% using median nerve stimulation in rats at 3 Hz and propofol as the anesthetic agent. At 6 Hz the activation was slightly but not statistically significantly greater. The feasibility of fMRI studies in animals using propofol suggests that it may be a useful anesthetic for fMRI studies in agitated adult patients or in children.

An NMR method is presented for separating blood volume and magnetic susceptibility effects in response to respiratory challenges such as hypoxia and hyperoxia. The technique employs high susceptibility contrast agents to enhance blood volume induced signal changes. The results show that for a rat model the dominant source of signal variation upon changing breathing gas from 100% oxygen to 10% oxygen/90% nitrogen is the change in blood magnetic susceptibility associated with the BOLD effect. The results imply that signal changes associated with respiratory challenges can be regarded as indicators of local blood oxygenation in vivo.

Single-photon emission tomographic (SPET) imaging with the radiotracer [123I]2ß-carbomethoxy-3ß-(4-iodophenyl)tropane ([123I]ß-CIT) has been reported to be a useful in vivo measure of dopamine (DA) transporters. However, in addition to its high DA transporter affinity,ß-CIT also binds with high affinity to serotonin (5-HT) transporters. 2ß-Carboisopropoxy-3ß-(4-iodophenyl)tropane (IPCIT) has been demonstrated by in vitro studies to have higher selectivity for the DA transporter. We compared [123I]ß-CIT and [123I]IPCIT SPET imaging and plasma metabolite analyses in baboons to evaluate the potential advantages of [123I]IPCIT for quantitative in vivo measurements of DA transporter densities. Both tracers had low levels (2% of total plasma123I activity) of lipophilic radiolabeled metabolites at 420 min. [123I]IPCIT had significantly higher binding to plasma proteins. The average percent free (nonprotein bound) [123I]ß-CIT and [123I]IPCIT were 52%±7% and 14%±6%, respectively. Region of interest uptake data were normalized by injected dose and body weight. Consistent with the high density of 5-HT transporters in the midbrain and the lower 5-HT transporter affinity of IPCIT, the normalized peak specific midbrain uptake of [123I]ß-CIT (1.7±0.5) was higher than that of [123I]IPCIT (0.4±0.2). Consistent with its greater lipophilicity, [123I]IPCIT had higher nonspecific uptake, such that normalized cerebellar uptake of [123I]IPCIT was about twice that of [123I]ß-CIT. The ratio of specific to nonspecific uptake in striatum was greater for [123I]ß-CIT compared to [123I]IPCIT; however, striatal binding potentials and distribution volumes were not significantly different. In conclusion, [123I]IPCIT demonstrated in vivo a higher DA transporter selectivity and higher level of nonspecific uptake.