Arterial Spin Labeling Characterization of Cerebral Perfusion during Normal Maturation from Late Childhood into Adulthood: Normal ‘Reference Range’ Values and Their Use in Clinical Studies

Abstract

The human brain changes structurally and functionally during adolescence, with associated alterations in cerebral perfusion. We performed dynamic arterial spin labeling (ASL) magnetic resonance imaging in healthy subjects between 8 and 32 years of age, to investigate changes in cerebral hemodynamics during normal development. In addition, an inversion recovery sequence allowed quantification of changes in longitudinal relaxation time (T1) and equilibrium longitudinal magnetization (M0). We present mean and reference ranges for normal values of T1, M0, cerebral blood flow (CBF), bolus arrival time, and bolus duration in cortical gray matter, to provide a tool for identifying age-matched perfusion abnormalities in this age range in clinical studies. Cerebral blood flow and T1 relaxation times were negatively correlated with age, without gender or hemisphere differences. The same was true for M0 anteriorly, but posteriorly, males but not females showed a significant decline in M0 with increasing age. Two examples of the clinical utility of these data in identifying age-matched perfusion abnormalities, in Sturge–Weber syndrome and sickle cell anemia, are illustrated.

Neurological Complications and MRI

“…Current guidelines state that those children should be transfused indefinitely [47], but the TCD with transfusions changing to hydroxyurea (TWiTCH) trial suggests that, for those with no MRA abnormality may be able to switch to hydroxyurea prophylaxis after a year of transfusion [48]. Hydroxyurea does appear to reduce TCD velocities even without prior blood transfusion [1]; so, in settings where TCD is available but blood transfusion is not possible or is considered hazardous, it is probably reasonable to start hydroxyurea while the results of controlled trials are awaited [49]. In adults with SCD, there are no validated methods to screen for the increased stroke risk, as TCD studies in adults with HbSS find lower velocities than in children and cannot accurately stratify the risk of stroke [50].…”

“…A French study showed incidence of SCI as 28.2% by 8 years and 37.4% by 14 years [66]. Although it was thought that rates plateau in childhood, there is now evidence of new SCI in older adolescence and adulthood [1,67]. In the London cohort followed from the mid-1990s [68], 30% (3/10 patients) were found to have new SCI after the age of 14, 17 and 21 years, respectively (Figures 2 and 3).…”

“…In acute ischaemia, an area of oedema in the brain has a rapid decline in proton density and appears hyperintense on DWI and decreased on an ADC map, persisting for 10-14 days post-event [72], which can differentiate acute stroke from more remote events [24]. Not all children with evidence of ASCIE progress to SCI on MRI [1,62], which strongly suggests acute ischaemia may be reversible.…”

“…In patients with chronic cerebrovascular pathology and stroke, dynamic susceptibility contrast MRI (DSC-MRI) has shown focal areas of reduced CBF and prolonged mean transit time in the affected corresponding to stroke-like lesions [29,97]. Studies have consistently shown elevated global cerebral blood flow (CBF) [98][99][100][101][102][103][104], in association with the elevated cerebral blood flow velocity [28], which may be both a response to and a risk factor for cerebral hypoxia [98,99] and related to low haematocrit [98] and haemoglobin and haemoglobin F [103]. Strouse et al [99] found a strong inverse correlation with CBF and both full-scale IQ and performance IQ, which may be more sensitive than CBF velocity measured by TCD [105].…”

“…Sickle cell disease (SCD) is the commonest cause of stroke in childhood [1,2]. Focal cerebral ischaemia due to arterial or venous compromise is rarely fatal but accounts for 70-80% of all strokes [3][4][5] and nearly all episodes in children younger than 15 and adults older than 30 years.…”