Ferumoxytol-weighted MRI reveals heterogeneous vascularity in the macaque brain.

Representative 3D gradient-echo images (A) before and (B) after the ferumoxytol contrast agent injection. Green arrow indicates a sharp signal-intensity transition at the V1/V2 border. Cyan arrow indicates a thin sheet of sparse vasculature in the white matter underneath the gray matter of V1. (C) Ferumoxytol induced change in transverse relaxation rate (ΔR2*) displayed on subcortical and cortical midthickness gray matter (N=1). Average (D) pre-ferumoxytol R2*and (E) ΔR2* equivolumetric layers (ELs; N=4). (F) Histograms in selected brain regions and (G) ELs. Solid lines and shadow indicate mean and standard deviation (N=4), respectively. Abbreviations: CAU: Caudate nucleus; PUT: Putamen; TH: Thalamus; IC: Inferior colliculus; CBX: Cerebellar cortex. Data at https://balsa.wustl.edu/TBA.

Estimated transverse relaxation rate (R2*) before and after injection of ferumoxytol contrast agent. Values are mean (std) (N=4). Abbreviations: WM white matter.

Charting large-caliber vessel networks in the cerebral cortex.

(A) Ferumoxytol-weighted MRI reveals a continuous pial vessel network running along the cortical surface. Note that the large vessels branch into smaller pial vessels. (B) Cortical surface mapping of intra-cortical vessels. Vessels were identified using high-frequency gradients (red-yellow colors) and each blue dot indicates the vessel’s central location. Representative equivolumetric layer (EL) 4a is displayed on a 656k surface mesh. (C) Number of penetrating vessels across ELs per hemisphere. Solid lines and shadow show mean and standard deviation across TEs (N=1). (D) Non-uniformly sampled Lomb-Scargle geodesic-distance periodogram. The vessels exhibit a peak frequency at about 0.6 1/mm reflecting the frequency of large-caliber vessels. (E) Comparison of vessel density in V1 determined using MRI (current study) and ‘ground-truth’ anatomy. In volume space, the density of vessels was estimated using Frangi-filter whereas in the surface mesh the density was estimated using local minima. These are compared to the density of penetrating vessels with a diameter of 20-50 μm (Zheng et al., 1991) and the density of feeding arterial and draining veins evaluated using fluorescence microscopy (Weber et al., 2008).

Exemplar laminar profiles of transverse relaxation rate (R2*) and ferumoxytol induced change in R2 (ΔR2*) in the macaque cerebral cortex.

(A) Exemplar equivolumetric layer 4b (EL4b) R2* and (B) ΔR2* displayed on cortical flat-map. Note that primary sensory areas (e.g. V1, A1, area 3) and association areas exhibit high and low ΔR2*, respectively. (C, D) Exemplar laminar profiles from visual cortical areas. Solid lines and shadow show mean and standard deviation across hemispheres, respectively. (E) Laminar ΔR2* profiles relative to the V1. Solid lines and shadow show mean and inter-subject standard deviation. (F) Peak-normalized ΔR2* profile compared with anatomical ground-truth in V1 (Weber et al., 2008). Cytochrome-c oxidase (CO) activity, capillary and large vessel volume fractions were estimated from their Figure 4. Abbreviations: A1: primary auditory cortex; A7 Brodmann area 7; MT middle temporal area; V1: primary visual cortex; V2: secondary visual cortex; 3: primary somatosensory cortex; 4: primary motor cortex.

Variations in vascular network architecture reveal cortical area boundaries.

(A) Ferumoxytol induced change in transverse relaxation rate (ΔR2*) displayed at a representative equivolumetric layer 4b (EL4b) (N=4). Overlaid black lines show exemplary M132 atlas area boundaries. (B) ΔR2* gradients co-align with exemplary areal boundaries. Red arrow indicates an artifact from inferior sagittal sinus. Average (C) mid-thickness weighted T1w/T2w-FLAIR myelin and (D) cortical thickness maps. Data at https://balsa.wustl.edu/TBA.

Hierarchical organization and principal types of cerebral vasculature.

(A) Average ΔR2* equivolumetric layers (ELs) ascending from pial surface (left) to white matter surface (right) (N=4; hemispheres=8). Parcel order was sorted by (B) dendrogram determined using Wards’ method. (C) Similarity matrix as estimated using Euclidean distance. (D) Clusters displayed on a cortical flat-map. (E) Average cluster profiles. Error-bar indicates standard deviation across parcels within each cluster. (F) Cytoarchitectonic structural type co-vary with ΔR2*.

The anatomical underpinnings of the vascular network architecture.

(A) Neuron (Collins et al., 2010), (B) total receptor density (Froudist-Walsh et al., 2023), (C, D) R2* and ΔR2* (current study). Multiple linear regression model was used to investigate the relationship between neuron and total receptor densities and (E) baseline R2* and (F) ΔR2* across layers. T-values are threshold at significance level (p < 0.05, Bonferroni corrected). Data at https://balsa.wustl.edu/TBA.