Shaolin Yang

CEST signal at 2ppm (CEST@2ppm) from Z-spectral fitting correlates with creatine distribution in brain tumor.

In general, multiple components such as water direct saturation, magnetization transfer (MT), chemical exchange saturation transfer (CEST) and aliphatic nuclear Overhauser effect (NOE) contribute to the Z‐spectrum. The conventional CEST quantification method based on asymmetrical analysis may lead to quantification errors due to the semi‐solid MT asymmetry and the aliphatic NOE located on a single side of the Z‐spectrum. Fitting individual contributors to the Z‐spectrum may improve the quantification of each component. In this study, we aim to characterize the multiple exchangeable components from an intracranial tumor model using a simplified Z‐spectral fitting method. In this method, the Z‐spectrum acquired at low saturation RF amplitude (50 Hz) was modeled as the summation of five Lorentzian functions that correspond to NOE, MT effect, bulk water, amide proton transfer (APT) effect and a CEST peak located at +2 ppm, called CEST@2ppm. With the pixel‐wise fitting, the regional variations of these five components in the brain tumor and the normal brain tissue were quantified and summarized. Increased APT effect, decreased NOE and reduced CEST@2ppm were observed in the brain tumor compared with the normal brain tissue. Additionally, CEST@2ppm decreased with tumor progression. CEST@2ppm was found to correlate with the creatine concentration quantified with proton MRS. Based on the correlation curve, the creatine contribution to CEST@2ppm was quantified. The CEST@2ppm signal could be a novel imaging surrogate for in vivo creatine, the important bioenergetics marker. Given its noninvasive nature, this CEST MRI method may have broad applications in cancer bioenergetics. Copyright

Quantitative Tract-Specific Measures of Uncinate and Cingulum in Major Depression Using Diffusion Tensor Imaging

Previous findings suggested the role of the prefrontal cortex, hippocampus, and cingulate gyrus in major depressive disorders (MDD), but the white matter microstructural abnormalities of the fibers connecting these brain structures are not known. The purpose of this study was to test the hypothesis that white matter abnormalities are present in association fibers of the uncinate fasciculus (UF) and cingulum bundle (CB) among MDD subjects. A total of 21 MDD subjects aged between 30 and 65 years and 21 age-matched healthy controls (HC) were recruited. All subjects were right-handed and without history of diabetes or other cardiac diseases. We extracted quantitative tract-specific measures based on diffusion tensor imaging tractography to examine both diffusivity and geometric properties of the UF and CB. Significantly decreased fractional anisotropy (FA) and increased radial diffusivity of the right UF were observed in MDD patients compared with HC (p<0.05), while their geometric characteristics remained relatively unchanged. Among MDD subjects, depression severity had a significant negative correlation with normalized number of fibers (NNF) in the right UF (r=−0.53, p=0.02). We also found significant age effect (old<young) in HC group and laterality effect (L>R) in both groups in the FA measure of the CB. Our study demonstrates novel findings of white matter microstructural abnormalities of the right UF in MDD. In the MDD group, the severity of depression is associated with reduced NNF in the right UF. These findings have implications for both clinical manifestations of depression as well as its pathophysiology.

Spectral simplification for resolved glutamate and glutamine measurement using a standard STEAM sequence with optimized timing parameters at 3, 4, 4.7, 7, and 9.4T

The C4 multiplet proton resonances of glutamate (Glu) around 2.35 ppm and glutamine (Gln) around 2.45 ppm usually overlap in MR spectra, particularly at low‐ and mid‐field strengths (1.5–4.7T). A spectral simplification approach is introduced that provides unobstructed Glu and Gln measurement using a standard STEAM localization sequence with optimized interpulse timings. The underlying idea is to exploit the dependence of response of a coupled spin system on the echo time (TE) and mixing time (TM) to find an optimum timing set (TE, TM), at which the outer‐wings of C4 “pseudo‐triplet” proton resonances of Glu and Gln are significantly suppressed while the central peaks are maintained. The spectral overlap is thus resolved as the overlap exists exclusively at the outer‐wings and the central peaks are readily separated due to the approximate 0.1‐ppm difference in chemical shift. Density matrix simulation for Glu, Gln, and other overlapping metabolites at 2.3–2.5 ppm was conducted to predict the optimum timing sets. The simulated, phantom, and in vivo results demonstrated that the C4 multiplet proton resonances of Glu and Gln can be resolved for unobstructed detection at 3T, 4T, and 4.7T. For simplicity, only simulated data are illustrated at 7T and 9.4T. Magn Reson Med 59:236–244, 2008.

Lower glutamate levels in rostral anterior cingulate of chronic cocaine users — A 1H-MRS study using TE-averaged PRESS at 3 T with an optimized quantification strategy

Previous studies have shown significantly lower metabolism and functional activity in the anterior cingulate cortex (ACC) of human cocaine addicts. The present study examined whether this ACC hypoactivity is associated with altered glutamate (Glu), the primary excitatory neurotransmitter in the central nervous system (CNS), which has been recently implicated in drug addiction. Participants comprised 14 chronic cocaine addicts and 14 matched healthy volunteers who were examined using (1)H magnetic resonance spectroscopy at 3 T. A new quantification strategy for echo time (TE)-averaged point-resolved spectroscopy (PRESS) was applied to disentangle relaxation effects from J-evolution of coupled spin systems such as Glu. The concentrations of Glu as well as N-acetyl aspartate (NAA), total creatine (tCr), choline-containing compounds (tCho), and myo-inositol (Ins) were estimated from both groups. Glu/tCr was significantly lower in chronic cocaine users compared to control subjects and was significantly correlated with years of cocaine use. Glu/tCr was also positively correlated with NAA/tCr. NAA/tCr significantly decreased with age but was not significantly different between the two groups. These findings suggest a metabolic/neurotransmitter dysregulation associated with cocaine addiction and support a possible therapeutic intervention strategy aimed at normalizing the Glu transmission and function in the treatment of cocaine addiction.

In Vivo Assessment of Neurotransmitters and Modulators with Magnetic Resonance Spectroscopy: Application to Schizophrenia

In vivo measurement of neurotransmitters and modulators is now feasible with advanced proton magnetic resonance spectroscopy ((1)H MRS) techniques. This review provides a basic tutorial of MRS, describes the methods available to measure brain glutamate, glutamine, γ-aminobutyric acid, glutathione, N-acetylaspartylglutamate, glycine, and serine at magnetic field strengths of 3T or higher, and summarizes the neurochemical findings in schizophrenia. Overall, (1)H MRS holds great promise for producing biomarkers that can serve as treatment targets, prediction of disease onset, or illness exacerbation in schizophrenia and other brain diseases.

Graph Theory Analysis of Cortical-Subcortical Networks in Late-Life Depression

OBJECTIVES Late-life major depression (LLD) is characterized by distinct epidemiologic and psychosocial factors, as well as medical comorbidities that are associated with specific neuroanatomical differences. The purpose of this study was to use interregional correlations of cortical and subcortical volumes to examine cortical-subcortical structural network properties in subjects with LLD compared with healthy comparison subjects. METHODS This was a cross-sectional neuroimaging study conducted in the general community. We recruited 73 healthy elderly comparison subjects and 53 subjects with LLD who volunteered in response to advertisements. Brain network connectivity measures were generated by correlating regional volumes after controlling for age, gender, and intracranial volume by using the Brain Connectivity Toolbox. RESULTS Results for overall network strength revealed that LLD networks showed a greater magnitude of associations for both positive and negative correlation weights compared with healthy elderly networks. LLD networks also demonstrated alterations in brain network structure compared with healthy comparison subjects. LLD networks were also more vulnerable to targeted attacks compared with healthy elderly comparison subjects, and this vulnerability was attenuated when controlling for white matter alterations. CONCLUSIONS Overall, this study demonstrates that cortical-subcortical network properties are altered in LLD and may reflect the underlying neuroanatomical vulnerabilities of the disorder.

Development of superficial white matter and its structural interplay with cortical gray matter in children and adolescents

Healthy human brain undergoes significant changes during development. The developmental trajectory of superficial white matter (SWM) is less understood relative to cortical gray matter (GM) and deep white matter. In this study, a multimodal imaging strategy was applied to vertexwise map SWM microstructure and cortical thickness to characterize their developmental pattern and elucidate SWM‐GM associations in children and adolescents. Microscopic changes in SWM were evaluated with water diffusion parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in 133 healthy subjects aged 10–18 years. Results demonstrated distinct maturational patterns in SWM and GM. SWM showed increasing FA and decreasing MD and RD underneath bilateral motor sensory cortices and superior temporal auditory cortex, suggesting increasing myelination. A second developmental pattern in SWM was increasing FA and AD in bilateral orbitofrontal regions and insula, suggesting improved axonal coherence. These SWM patterns diverge from the more widespread GM maturation, suggesting that cortical thickness changes in adolescence are not explained by the encroachment of SWM myelin into the GM‐WM boundary. Interestingly, age‐independent intrinsic association between SWM and cortical GM seems to follow functional organization of polymodal and unimodal brain regions. Unimodal sensory areas showed positive correlation between GM thickness and FA whereas polymodal regions showed negative correlation. Axonal coherence and differences in interstitial neuron composition between unimodal and polymodal regions may account for these SWM‐GM association patterns. Intrinsic SWM‐GM relationships unveiled by neuroimaging in vivo can be useful for examining psychiatric disorders with known WM/GM disturbances. Hum Brain Mapp 35:2806–2816, 2014.

White Matter Tract Integrity in Late-Life Depression: Associations with Severity and Cognition

BACKGROUND Although significant changes in both gray and white matter have been noted in late-life depression (LLD), the pathophysiology of implicated white-matter tracts has not been fully described. In this study we examined the integrity of specific white-matter tracts in LLD versus healthy controls (HC). METHOD Participants aged ⩾60 years were recruited from the community. The sample included 23 clinically diagnosed individuals with LLD and 23 HC. White-matter integrity metrics [fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD)] were calculated in the bilateral cingulum and uncinate fasciculus. Depression severity was measured using the Center for Epidemiological Studies Depression Scale (CESD). Composite scores for learning and memory and executive function were created using standardized neuropsychological assessments. RESULTS White-matter integrity was lower in LLD versus HC in the bilateral cingulum and right uncinate fasciculus (p⩽0.05). In the whole sample, depression severity correlated with integrity in the bilateral cingulum and right uncinate fasciculus (p ⩽0.05). In patients, depression severity correlated with the integrity of the left uncinate fasciculus (p = 0.03); this tract also correlated with executive function (p = 0.02). Among HC, tract integrity did not correlate with depression scores; however, learning and memory correlated with integrity of the bilateral uncinate fasciculus and bilateral cingulum; executive function correlated with the right uncinate and left cingulum (p ⩽0.05). CONCLUSIONS White-matter tract integrity was lower in LLD than in HC and was associated with depression severity across all participants. Tract integrity was associated with cognition in both groups but more robustly among HC.

Head motion suppression using real-time feedback of motion information and its effects on task performance in fMRI.

A voluntary head motion suppression method using feedback to subjects of their own head motion information is demonstrated. A real-time fMRI system was developed on standard MR imaging hardware for this purpose. The head motion information was simplified as a four-way arrow display that changed color from green to red when a composite head motion index went beyond a specified threshold. The arrow indicators were integrated into a version of the commonly used visual N-BACK task. Results suggest a significant suppression of head motion consistently in all subjects while the influence on task performance and brain activation was minimal. It is proposed that under certain experimental conditions, voluntary head motion suppression may feasibly be employed without significant compromise of fMRI data.

Multimodal Brain Connectivity Analysis in Unmedicated Late-Life Depression

Late-life depression (LLD) is a common disorder associated with emotional distress, cognitive impairment and somatic complains. Structural abnormalities have been suggested as one of the main neurobiological correlates in LLD. However the relationship between these structural abnormalities and altered functional brain networks in LLD remains poorly understood. 15 healthy elderly comparison subjects from the community and 10 unmedicated and symptomatic subjects with geriatric depression were selected for this study. For each subject, 87 regions of interest (ROI) were generated from whole brain anatomical parcellation of resting state fMRI data. Whole-brain ROI-wise correlations were calculated and compared between groups. Group differences were assessed using an analysis of covariance after controlling for age, sex and education with multiple comparison correction using the false discovery rate. Structural connectivity was assessed by tract-based spatial statistics (TBSS). LLD subjects had significantly decreased connectivity between the right accumbens area (rA) and the right medial orbitofrontal cortex (rmOFC) as well as between the right rostral anterior cingulate cortex (rrACC) and bilateral superior frontal gyrus (bsSFG). Altered connectivity of rrACC with the bsSFG was significantly correlated with depression severity in depressed subjects. TBSS analysis showed a 20% reduction in fractional anisotropy (FA) in the right Forceps Minor (rFM) in depressed subjects. rFM FA values were positively correlated with rA-rmOFC and rrACC-bsFG functional connectivity values in our total study sample. Coordinated structural and functional impairment in circuits involved in emotion regulation and reward pathways play an important role in the pathophysiology of LLD.