作者: Teresa R. Franklin , Reagan R. Wetherill , Kanchana Jagannathan , Nathan Hager , Charles P. O'Brien
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摘要: The magnetization-prepared rapid gradient-echo (MP-RAGE) T1-weighted high resolution structural MRI is a mainstay tool used to identify morphometric biomarkers of disease conditions, progression and treatment effects despite critical limitation: the relaxation signal on which inferences are based nearly indistinguishable for gray matter vs. blood flow (Lu et al., 2004; Wright 2008). Thus, apparent reported findings might be at least partially related transient changes in or other physiological signals. Consistent with this technical limitation, using standard analysis technique, voxel morphometry (VBM), we recently that single dose medication had “apparent” MRIs (Franklin 2013). Specifically, observed medication-induced decreases volume anterior cingulate regions overlapped brain (perfusion). Similarly, others have shown scans likely transient. For example, acute levodopa administration altered indices images midbrain (Salgado-Pineda 2006). Further, well-controlled longitudinal VBM study patients attention deficit hyperactivity disorder (ADHD), Hoekzema al. (2014) showed stimulant drugs trigger volumetric ventral striatum, challenging previous studies suggesting these were an intrinsic feature (Hoekzema 2014). These examples highlight importance employing appropriate experimental conditions ensure actually revealing long-term unrelated states. investigations into neural structure may want include group administered medication. The induced by pharmacological manipulations highlighted above led us hypothesize cigarette smoking, delivers psychostimulant, nicotine, transiently alter MP-RAGE, images. examined acquired within-subjects design 39 otherwise healthy nicotine-dependent individuals. Subjects meeting our MRI-specific inclusion/exclusion criteria 2013, 2014) provided written informed consent participate study, adhered Declaration Helsinki was approved University Pennsylvania Institutional Review Board. Screening procedures included medical history, physical examination, psychological assessment. participated two counterbalanced scanning sessions occurred separate days. condition “Smoke” subjects smoked satiety approximately 45 min prior obtaining data. “No smoke,” then remained abstinent 5 h data acquisition. To obtain quantitative cerebral (CBF) maps, resting baseline pseudo-continuous arterial spin labeled perfusion fMRI also under both conditions. Nicotine's terminal half-life 2 h; thus, conservative estimates place onset withdrawal symptomatology within first after last smoking (Benowitz 1982). deprivation chosen would experiencing from nicotine. During smoke” condition, carbon monoxide (CO) levels scanning. Abstinence confirmed monitoring biochemically observing reductions CO time scan Structural analyzed statistical mapping software (SPM8) its available diffeomorphic anatomical registration exponentiated lie algebra (DARTEL). Statistical parametric maps generated perform between-condition comparisons (paired t-test) tissue segmentation output DARTEL. measures mean CBF calculated each performed. Image acquisition, processing methods been previously published 2014). Once again, report state impacts indices. Compared not several hours, recent T-1 weighted bilaterally striatum (see Figure Figure11 http://www.franklinbrainimaging.com/LimitationsofMPRAGE/, provides all 3 planes). Differences any regions. Additionally, as (Figure S1 shows results MP-RAGE overlain same template. unambiguously demonstrate use must employ states introduced drug medication, but indeed change. Importantly, medications substances (e.g., alcohol, cigarettes, concomitant medications) affect should controlled (either through matching co-variation) across groups being compared. Third, show initiation session, given potential it subsequent activities (tasks, manipulations) occur over course underscore crucial immediate need develop neuroimaging tools can uniquely capture neuronal dissociable those signals. Figure 1 Illustration results. MPRAGE individuals (Smoke condition) maintaining monitored abstinence (No Smoke ...