Cerebral Blood Flow Biomarkers of Autism during a Passive Viewing Task

Background:  Changes in the cerebral blood flow (CBF) reflect underlying neural activation (Sokoloff, 1981).  One MRI based-method for characterizing CBF, Arterial Spin Labeling (ASL), relies on the magnetic tagging of cerebral blood water for weighted measures of relative CBF across the entire brain. Compared to the fMRI based BOLD signal, ASL is more sensitive to small changes in CBF over the course of several minutes (Aguirre et al., 2002; Wang et al., 2003). Despite this advantage, there are no published brain imaging studies of autism using ASL.

Objectives:  Evaluate brain perfusion in ASD compared to matched typically developing controls (TDC) during passive watching of a nature video.

Methods:  Thirty-three males with ASD and 26 TDC males, matched on age (ASD=14.9 ± 1.7, TDC=14.9 ± 1.64, p=0.97) were scanned with pseudo-continuous ASL (pCASL) at 3T, while watching without sound the Discovery Channel video (“Planet Earth: Pole-to-Pole”) on a projection screen. All participants were re-scanned while watching this video about 10 weeks later (ASD= 9.68 ± 2.64, TDC=11.08 ± 4.28) in order to assess per-voxel regional CBF (rCBF) reliability via intra-class correlation (ICC).  rCBF (mL/100g/min) was measured using pCASL with 2D gradient-echo echo-planar imaging (GE EPI). The labeling and control RF duration was 1.5 sec with post-labeling delay of 1.2 sec. Multi-slice perfusion maps with 40 label/control pairs were acquired with: TR/TE = 4000/17 ms, flip angle=90⁰, bandwidth = 3005 Hz/pixel, slice thickness = 5mm, matrix size = 64×64, FOV = 220×220 mm² and slice number = 20).

Results:  Gray matter signal was moderate-to-highly reliable (ICCs: 0.5 to > 0.9), with no significant group differences in ICC values. Per-voxel group comparisons of rCBF averaged across both time points revealed robust ventral pathway deficits in ASD (p < 0.05 corrected) extending posteriorly from the temporal pole to the fusiform and middle temporal gyri in both hemispheres (Fig 1). Left hemisphere reductions in rCBF were particularly robust, especially the left temporal pole (p<0.006 corrected). No evidence of ASD hyper-perfusion (ASD > TDC; p < 0.05 corrected) was observed. Group differences were found for several phenotypic measures of behavior (e.g. SRS, Vineland), and these metrics strongly correlated  (r’s > .68) with left temporal pole rCBF.

Conclusions:  To our knowledge this is the first demonstration of rCBF perfusion deficits in ASD.  This method is very promising for characterizing biomarkers, as it is reliable across the duration of a typical drug trial, takes only ~ 8 minutes to collect, does not require compliance with an active task, and yields robust group differences. Findings were concentrated in the temporal lobes, and include hypoperfusion of the fusiform face and word form areas (with the former being localized individually via fMRI for each participant).  These results also highlight the role of the temporal pole in socially relevant integrative processes (See Olsen et al., 2007 review).