Arterial spin labeling perfusion MRI in pediatric arterial ischemic stroke: initial experiences.

PURPOSE: To investigate the feasibility and utility of arterial spin labeling (ASL) perfusion MRI for characterizing alterations of cerebral blood flow (CBF) in pediatric patients with arterial ischemic stroke (AIS). MATERIALS AND METHODS: Ten children with AIS were studied within 4 to 125 hours following symptom onset, using a pulsed ASL (PASL) protocol attached to clinically indicated MR examinations. The interhemisphere perfusion deficit (IHPD) was measured in predetermined vascular territories and infarct regions of restricted diffusion, which were compared with the degree of arterial stenosis and volumes of ischemic infarcts. RESULTS: Interpretable CBF maps were obtained in all 10 patients, showing simple lesion in nine patients (five hypoperfusion, two hyperperfusion, and two normal perfusion) and complex lesions in one patient. Both acute and follow-up infarct volumes were significantly larger in cases with hypoperfusion than in either hyper- or normal perfusion cases. The IHPD was found to correlate with the degree of stenosis, diffusion lesion, and follow-up T(2) infarct volumes. Mismatch between perfusion and diffusion lesions was observed. Brain regions presenting delayed arterial transit effects were tentatively associated with positive outcome. CONCLUSION: This study demonstrates the clinical utility of ASL in the neuroimaging diagnosis of pediatric AIS.

Why perfusion in neonates with congenital heart defects is negative--technical issues related to pulsed arterial spin labeling.

Pulsed arterial spin labeling (PASL) perfusion MRI has unique advantages for measuring cerebral blood flow (CBF) in the pediatric population. In neonates with congenital heart defects (CHDs), however, a considerable number of negative CBF values were observed in PASL perfusion images. A set of specific physiological and biophysical conditions were proposed as plausible explanations for this phenomenon, including small body size, low blood flow, prolonged tracer life time (blood T1) and the "shunt" between pulmonary and systemic circulations in CHD. An optimized PASL scheme with a restricted label volume was proposed, and experimental data demonstrated reduced spurious negative values and lower intersubject variability of perfusion measurements in neonates with CHD as compared to standard PASL sequences.

Preoperative cerebral blood flow is diminished in neonates with severe congenital heart defects.

OBJECTIVE: Impaired neurodevelopmental outcome represents a major morbidity for survivors of infant heart surgery for congenital heart defects. Previous studies in these neonates have reported preoperative microcephaly, periventricular leukomalacia, and other findings. The hypothesis of this study is that preoperative cerebral blood flow is substantially diminished and might relate to preoperative neurologic conditions. METHODS: Preoperative brain magnetic resonance imaging was performed. Cerebral blood flow measurements in infants with congenital heart defects were obtained by using a novel noninvasive magnetic resonance imaging technique, pulsed arterial spin-label perfusion magnetic resonance imaging. Cerebral blood flow was measured before the operation under standard ventilation and repeated after increased carbon dioxide. RESULTS: A total of 25 term infants were studied. The average age at the time of the operation was 4.4 +/- 4.6 days. Congenital heart defects varied widely. Microcephaly occurred in 24% (6/25). Baseline cerebral blood flow was 19.7 +/- 9.2 mL . 100 g -1 . min -1 (8.0-42.2 mL . 100 g -1 . min -1 ). Five patients had cerebral blood flow measurements of less than 10 mL . 100 g -1 . min -1 . Mean hypercarbic cerebral blood flow increased to 40.1 +/- 20.3 mL . 100 g -1 . min -1 (11.4-94.0 mL . 100 g -1 . min -1 , P < .001). Pairwise analyses found that low hemoglobin levels were associated with higher baseline cerebral blood flow values ( P = .04). Periventricular leukomalacia occurred in 28% (7/25) and was associated with decreased baseline cerebral blood flow values ( P = .05) and a smaller change in cerebral blood flow with hypercarbia ( P = .003). CONCLUSIONS: Structural brain abnormalities are common in these neonates before surgical intervention. Preoperative cerebral blood flow for this cohort was low and drastically reduced in some patients. Low cerebral blood flow values were associated with periventricular leukomalacia. Carbon dioxide reactivity was preserved but might be compromised by some aspects of the cardiac anatomy. The full spectrum of cerebral blood flow measurements with this technique in congenital heart defects and their long-term significance require continued investigation.

Novel insights into the regulation of the timeless protein.

In the Drosophila circadian clock, period (per) and its partner, timeless (tim), play a central role in the negative limb of an autoregulatory feedback loop. Unlike per, the dosage of which affects the frequency (tau) of the circadian cycle, we found that increasing copies of the tim gene has no effect on clock period length. The use of the tim promoter to express per results in a shortening of circadian period, also indicating that the regulation of tim is different from that of per. Drosophila TIM is similar to the mammalian circadian protein mPER2 in that it shuttles independently between the nucleus and cytoplasm both in vivo and in vitro. Contrary to the current model that PER and TIM heterodimerization is a prerequisite for their nuclear entry, PER is not required to transport TIM into nuclei, although it influences TIM localization and vice versa. Blocking nuclear export led to increased nuclear expression of TIM in S2 cells and in wild-type and per01 larvae, suggesting that PER may be required for nuclear retention of TIM. Unlike PER, nuclear TIM alone has no ability to repress transcription. We propose that TIM drives cycles of PER expression by regulating its stability, and in turn, PER retains TIM in the nucleus, either for the regulation of its own stability or for a novel nuclear role of TIM.