Cortical parcellation based on resting fMRI is an important tool for investigating the functional organization and connectivity of the cerebral cortex. Group parcellation based on co-registration of anatomical images to a common atlas will inevitably result in errors in the locations of the boundaries of functional parcels when they are mapped back from the atlas to the individual. This is because areas of functional specialization vary across individuals in a manner that cannot be fully determined from the sulcal and gyral anatomy that is used for mapping between atlas and individual. We describe a method that avoids this problem by refining an initial group parcellation so that for each subject the parcel boundaries are optimized with respect to that subject’s resting fMRI. Initialization with a common parcellation results in automatic correspondence between parcels across subjects. Further, by using a group sparsity constraint to model connectivity, we exploit group similarities in connectivity between parcels while optimizing their boundaries for each individual. We applied this approach with initialization on both high and low density group cortical parcellations and used resting fMRI data to refine across a group of individuals. Cross validation studies show improved homogeneity of resting activity within the refined parcels. Comparisons with task-based localizers show consistent reduction of variance of statistical parametric maps within the refined parcels relative to the group-based initialization indicating improved delineation of regions of functional specialization. This method enables a more accurate estimation of individual subject functional areas, facilitating group analysis of functional connectivity, while maintaining consistency across individuals with a standardized topological atlas.

Stroke is common in children with sickle cell disease and results from an imbalance in oxygen supply and demand. Cerebral blood flow (CBF) is increased in patients with sickle cell disease to compensate for their anemia, but adequacy of their oxygen delivery has not been systematically demonstrated. This study examined the physiological determinants of CBF in 37 patients with sickle cell disease, 38 ethnicity matched control subjects and 16 patients with anemia of non-sickle origin. Cerebral blood flow was measured using phase contrast MRI of the carotid and vertebral arteries. CBF increased inversely to oxygen content (r2 = 0.69, p < 0.0001). Brain oxygen delivery, the product of CBF and oxygen content, was normal in all groups. Brain composition, specifically the relative amounts of grey and white matter, was the next strongest CBF predictor, presumably by influencing cerebral metabolic rate. Grey matter/white matter ratio and CBF declined monotonically until the age of 25 in all subjects, consistent with known maturational changes in brain composition. Further CBF reductions were observed with age in subjects older than 35 years of age, likely reflecting microvascular aging. On multivariate regression, CBF was independent of disease state, hemoglobin S, hemoglobin F, reticulocyte count and cell free hemoglobin, suggesting that it is regulated similarly in patients and control subjects. In conclusion, sickle cell disease patients had sufficient oxygen delivery at rest, but accomplish this only by marked increases in their resting CBF, potentially limiting their ability to further augment flow in response to stress.

Diffusion MRI provides quantitative information about microstructural properties which can be useful in neuroimaging studies of the human brain. Echo planar imaging (EPI) sequences, which are frequently used for acquisition of diffusion images, are sensitive to inhomogeneities in the primary magnetic (B0) field that cause localized distortions in the reconstructed images. We describe and evaluate a new method for correction of susceptibility-induced distortion in diffusion images in the absence of an accurate B0 fieldmap. In our method, the distortion field is estimated using a constrained non-rigid registration between an undistorted T1-weighted anatomical image and one of the distorted EPI images from diffusion acquisition. Our registration framework is based on a new approach, INVERSION (Inverse contrast Normalization for VERy Simple registratION), which exploits the inverted contrast relationship between T1-and T2-weighted brain images to define a simple and robust similarity measure. We also describe how INVERSION can be used for rigid alignment of diffusion images and T1-weighted anatomical images. Our approach is evaluated with multiple in vivo datasets acquired with a different acquisition parameters. Compared to other methods, INVERSION shows robust and consistent performance in rigid registration and shows improved alignment of diffusion and anatomical images relative to normalized mutual information for non-rigid distortion correction.

Sickle cell disease (SCD) is the most common cause of stroke in childhood and results primarily from a mismatch of cerebral oxygen supply and demand rather than arterial obstruction. However, resting cerebral blood flow (CBF) has not been examined in the general African American population, in whom obesity, hypertension, cerebrovascular disease, and diminished cerebrovascular reserve capacity are common. To better understand the underlying physiological substrate upon which SCD is superimposed, we measured CBF in 32 young (age 28 ± 10 yr), asymptomatic African American subjects with and without sickle cell trait (n= 14). To characterize the effects of chronic anemia, in isolation of sickle hemoglobin we also studied a cohort of 13 subjects with thalassemia major (n= 10), dyserythropoetic anemia (n= 1), or spherocytosis (n= 2). Blood was analyzed for complete blood count, hemoglobin electrophoresis, cell free hemoglobin, and lactate dehydrogenase. Multivariate regression analysis showed that oxygen content was the strongest predictor of CBF (r(2)= 0.33,P< 0.001). CBF declined rapidly in the second and third decades of life, but this drop was explained by reductions in cerebral gray matter. However, age effects persisted after correction for brain composition, possibly representing microvascular impairment. CBF was independent of viscosity, hemoglobin S%, and body mass index. Hyperoxia resulted in reduced CBF by 12.6% (P= 0.0002), and CBF changes were proportional to baseline oxygen content (r(2)= 0.16,P= 0.02). These data suggest that these hemoglobin subtypes do not alter the normal CBF regulation of the balance of oxygen supply and demand.

Although modern medical management has lowered overt stroke occurrence in patients with sickle cell disease (SCD), progressive white matter (WM) damage remains common. It is known that cerebral blood flow (CBF) increases to compensate for anemia, but sufficiency of cerebral oxygen delivery, especially in the WM, has not been systematically investigated. Cerebral perfusion was measured by arterial spin labeling in 32 SCD patients (age range: 10‐42 years old, 14 males, 7 with HbSC, 25 HbSS) and 25 age and race‐matched healthy controls (age range: 15‐45 years old, 10 males, 12 with HbAS, 13 HbAA); 8/24 SCD patients were receiving regular blood transfusions and 14/24 non‐transfused SCD patients were taking hydroxyurea. Imaging data from control subjects were used to calculate maps for CBF and oxygen delivery in SCD patients and their T‐score maps. Whole brain CBF was increased in SCD patients with a mean T‐score of 0.5 and correlated with lactate dehydrogenase (r2 = 0.58, P < 0.0001). When corrected for oxygen content and arterial saturation, whole brain and gray matter (GM) oxygen delivery were normal in SCD, but WM oxygen delivery was 35% lower than in controls. Age and hematocrit were the strongest predictors for WM CBF and oxygen delivery in patients with SCD. There was spatial co‐localization between regions of low oxygen delivery and WM hyperintensities on T2 FLAIR imaging. To conclude, oxygen delivery is preserved in the GM of SCD patients, but is decreased throughout the WM, particularly in areas prone to WM silent strokes.