Susceptibility artifact correction for sub-millimeter fMRI using inverse phase encoding registration and T1 weighted regularization.

BACKGROUND: Functional magnetic resonance imaging (fMRI) enables non-invasive examination of both the structure and the function of the human brain. The prevalence of high spatial-resolution (sub-millimeter) fMRI has triggered new research on the intra-cortex, such as cortical columns and cortical layers. At present, echo-planar imaging (EPI) is used exclusively to acquire fMRI data; however, susceptibility artifacts are unavoidable. These distortions are especially severe in high spatial-resolution images and can lead to misrepresentation of brain function in fMRI experiments. NEW METHOD: This paper presents a new method for correcting susceptibility artifacts by combining a T1-weighted (T1w) image and inverse phase-encoding (PE) based registration. The latter uses two EPI images acquired using identical sequences but with inverse-PE directions. In the proposed method, the T1w image is used to regularize the registration, and to select the regularization parameters automatically. The motivation is that the T1w image is considered to reflect the anatomical structure of the brain. RESULTS: Our proposed method is evaluated on two sub-millimeter EPI-fMRI datasets, acquired using 3T and 7T scanners. Experiments show that the proposed method provides improved corrections that are well-aligned to the T1w image. COMPARISON WITH EXISTING METHODS: The proposed method provides more robust and sharper corrections and runs faster compared with two other state-of-the-art inverse-PE based correction methods, i.e. HySCO and TOPUP. CONCLUSIONS: The proposed correction method used the T1w image as a reference in the inverse-PE registration. Results show its promising performance. Our proposed method is timely, as sub-millimeter fMRI has become increasingly popular.

Vascular effects on the BOLD response and the retinotopic mapping of hV4.

Despite general acceptance that the retinotopic organisation of human V4 (hV4) takes the form of a single, uninterrupted ventral hemifield, measured retinotopic maps of this visual area are often incomplete. Here, we test hypotheses that artefact from draining veins close to hV4 cause inverted BOLD responses that may serve to obscure a portion of the lower visual quarterfield-including the lower vertical meridian-in some hemispheres. We further test whether correcting such responses can restore the 'missing' retinotopic coverage in hV4. Subjects (N = 10) viewed bowtie, ring, drifting bar and full field flash stimuli. Functional EPIs were acquired over approximately 1.5h and analysed to reveal retinotopic maps of early visual cortex, including hV4. Normalised mean maps (which show the average EPI signal amplitude) were constructed by voxel-wise averaging of the EPI time course and used to locate venous eclipses, which can be identified by a decrease in the EPI signal caused by deoxygenated blood. Inverted responses are shown to cluster in these regions and correcting these responses improves maps of hV4 in some hemispheres, including restoring a complete hemifield map in one. A leftwards bias was found whereby 6/10 left hemisphere hV4 maps were incomplete, while this was the case in only 1/10 right hemisphere maps. Incomplete hV4 maps did not correspond with venous artefact in every instance, with incomplete maps being present in the absence of a venous eclipse and complete maps coexisting with a proximate venous eclipse. We also show that mean maps of upper surfaces (near the boundary between cortical grey matter and CSF) provide highly detailed maps of veins on the cortical surface. Results suggest that venous eclipses and inverted voxels can explain some incomplete hV4 maps, but cannot explain the remainder nor the leftwards bias in hV4 coverage reported here.

Regional differences in relaxation of electric field-stimulated canine airway smooth muscle by verapamil, isoproterenol and prostaglandin E2.

Regional differences in contraction produced by methacholine and electric field stimulation (EFS) and in relaxation produced by isoproterenol, prostaglandin E2 and verapamil were studied in isolated canine airway smooth muscle in vitro. Low-frequency EFS (3 Hz, 0.5 msec, 50 V) contracted thoracic trachealis to 43% of maximal EFS response, whereas cervical trachealis contracted to only 14% of maximum. EFS at 10 Hz produced 75% of the maximal response in both regions of the trachea. These EFS responses were abolished by 0.1 microM tetrodotoxin and 1.0 microM atropine. Contraction produced by EFS was also matched in each tissue by contraction with methacholine. The concentrations of methacholine that matched EFS at 10 Hz were 52 +/- 7, 378 +/- 84 and 66 +/- 11 nM for cervical and thoracic trachealis and lobar bronchi, respectively. Both EFS and matched methacholine contractions of cervical trachealis and lobar bronchi were completely relaxed by isoproterenol, whereas thoracic trachealis relaxed maximally to only 60% of induced tone. When verapamil was used to relax EFS and matched methacholine contractions, cervical trachealis was completely relaxed whereas thoracic trachealis relaxed to 15% of induced tone. Although there was a regional difference in the relaxant potency of isoproterenol and, to some extent, verapamil, there was no difference in isoproterenol or verapamil EC50 values for EFS vs. matched methacholine contractions within each region. In contrast, EFS contractions of thoracic trachealis were more sensitive to prostaglandin E2-induced relaxation than were matched methacholine contractions. These data demonstrate marked differences in cholinergic and beta adrenergic receptor-mediated responses between regions of the tracheobronchial tree.(ABSTRACT TRUNCATED AT 250 WORDS)

Methacholine sensitivity and cAMP protein kinase in tracheal smooth muscle.

We studied regional variation in canine trachealis smooth muscle sensitivity and responsiveness to methacholine as well as basal and methacholine-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) and cAMP-dependent protein kinase activity. The trachea between the cricoid cartilage and the carina was divided into three segments of equal length (designated cervical, middle, and thoracic regions), each consisting of approximately 12-14 cartilage rings. Smooth muscle strips from each of the three regions were exposed to cumulative half-log increments of methacholine chloride. The sensitivity (-log EC50) and responsiveness (force per cross-sectional area and force per milligram protein) of the smooth muscle to methacholine in each region was determined from these data. Smooth muscle strips from cervical and thoracic regions were frozen before and after exposure to cumulative half-log increments of methacholine up to each region's previously determined EC50. Frozen samples were assayed for cAMP content or cAMP-dependent protein kinase activity. The relationship between resting tension and methacholine sensitivity and responsiveness were studied. For the size strips we used, 4 g resting tension set the average cervical and thoracic strips at 96 and 101% of their optimal length, respectively. The methacholine EC50 was not affected by a variation in resting tension. Sensitivity to methacholine was 7.1, 6.8, and 6.5 for cervical, middle, and thoracic regions, respectively. The responsiveness of the cervical and thoracic smooth muscle to methacholine was 16.4 and 16.3 g force/mm2, respectively, at an EC50 methacholine. Basal cAMP was lower in cervical smooth muscle than in thoracic. cAMP-dependent protein kinase activity ratios under both basal and EC50 methacholine-stimulated conditions were lower in cervical smooth muscle than in thoracic. We have observed in trachealis smooth muscle an inverse relationship between methacholine sensitivity and either cAMP or cAMP-dependent protein kinase activity. We suggest that cAMP and cAMP-dependent protein kinase play a role in the regulation of airway smooth muscle sensitivity to cholinergic agonists.

Hydrocortisone and isoproterenol effects on trachealis cAMP and relaxation.

Isoproterenol concentration-response curves for cAMP formation and relaxation were determined in control and hydrocortisone-treated strips of canine tracheal smooth muscle. Adenosine 3'5'-cyclic monophosphate(cAMP) formation and muscle relaxation were well correlated, and both responses were enhanced proportionally by hydrocortisone treatment. Guanosine 3'5'-cyclic monophosphate was unchanged by isoproterenol but was increased to a small but significant extent by hydrocortisone. Prostaglandin E2 (not a beta-adrenergic agonist) relaxed the muscle strips, but this effect was not enhanced by hydrocortisone pretreatment. Our data are compatible with the concept that cAMP is an obligatory intermediate in the chain of events by which beta-adrenergic agonists relax airway smooth muscle. The action of hydrocortisone on this process is localized at or before cAMP formation, since it enhanced both cAMP formation and relaxation to the same extent.