The aim of this study was to implement a quantitative in vivo cardiac diffusion tensor imaging (DTI) technique that was robust, reproducible, and feasible to perform in patients with cardiovascular disease. A stimulated-echo single-shot echo-planar imaging (EPI) sequence with zonal excitation and parallel imaging was implemented, together with a novel modification of the prospective navigator (NAV) technique combined with a biofeedback mechanism. Ten volunteers were scanned on two different days, each time with both multiple breath-hold (MBH) and NAV multislice protocols. Fractional anisotropy (FA), mean diffusivity (MD), and helix angle (HA) fiber maps were created. Comparison of initial and repeat scans showed good reproducibility for both MBH and NAV techniques for FA (P > 0.22), MD (P > 0.15), and HA (P > 0.28). Comparison of MBH and NAV FA (FAMBHday1 = 0.60 ± 0.04, FANAVday1 = 0.60 ± 0.03, P = 0.57) and MD (MDMBHday1 = 0.8 ± 0.2 × 1023 mm2/s, MDNAVday1 = 0.9 ± 0.2 × 10−3 mm2/s, P = 0.07) values showed no significant differences, while HA values (HAMBHday1Endo = 22 ± 10°, HAMBHday1Mid-Endo = 20 ± 6°, HAMBHday1Mid-Epi = −1 ± 6°, HAMBHday1Epi = 17 ± 6°, HANAVday1Endo = 7 ± 7°, HAMBHday1Mid-Endo = 13 ± 8°, HAMBHday1Epi = −2 ± 7°, HAMBHday1Epi −14 ± 6°,) were significantly different. The scan duration was 20% longer with the NAV approach. Currently, the MBH approach is the more robust in normal volunteers. While the NAV technique still requires resolution of some bulk motion sensitivity issues, these preliminary experiments show its potential for in vivo clinical cardiac diffusion tensor imaging and for delivering high-resolution in vivo 3D DTI tractography of the heart.

Objective Abnormalities in the morphology and function of two gray matter structures central to emotional processing, the perigenual anterior cingulate cortex (pACC) and amygdala, have consistently been reported in bipolar disorder (BD). Evidence implicates abnormalities in their connectivity in BD. This study investigates the potential disruptions in pACC-amygdala functional connectivity and associated abnormalities in white matter that provides structural connections between the two brain regions, in BD. Methods Thirty-three individuals with BD and 31 healthy comparison participants (HC) participated in a scanning session during which functional magnetic resonance imaging (fMRI) during processing of face stimuli and diffusion tensor imaging (DTI) were performed. The strength of pACC-amygdala functional connections was compared between BD and HC groups, and associations between these functional connectivity measures from the fMRI scans and regional fractional anisotropy (FA) from the DTI scans were assessed. Results Functional connectivity was decreased between the pACC and amygdala in the BD group, compared to HC group, during the processing of fearful and happy faces (p<0.005). Moreover, a significant positive association between pACC-amygdala functional coupling and FA in ventrofrontal white matter including the region of the uncinate fasciculus was identified (p<0.005). Conclusion This study provides evidence for abnormalities in pACC-amygdala functional connectivity during emotional processing in BD. The significant association between pACC-amygdala functional connectivity and the structural integrity of white matter that contains pACC-amygdala connections suggest that disruptions in white matter connectivity may contribute to disturbances in the coordinated responses of the pACC and amygdala during emotional processing in BD.

Contrary to expectations derived from preclinical studies of the effects of stress, and imaging studies of adults with PTSD, there is no evidence of hippocampus atrophy in children with PTSD. Multiple pediatric studies have reported reductions in the corpus callosum -the primary white matter tract in the brain. Consequently, in the present study, Diffusion Tensor Imaging was used to assess corpus callosum white matter integrity in 17 maltreated children with PTSD and 15 demographically matched normal controls. Children with PTSD had reduced fractional anisotropy in the medial and posterior corpus, a region which contains interhemispheric projections from brain structures involved in circuits that mediate the processing of emotional stimuli and various memory functions ---core disturbances associated with a history of trauma. Further exploration of the effects of stress on corpus callosum and white matter development appears a promising strategy to better understanding the pathophysiology of PTSD in children.

Prenatal exposure to maternal smoking has been linked to cognitive and auditory processing deficits in offspring. Preclinical studies have demonstrated that exposure to nicotine disrupts neurodevelopment during gestation and adolescence, possibly by disrupting the trophic effects of acetylcholine. Given recent clinical and preclinical work suggesting that neurocircuits that support auditory processing may be particularly vulnerable to developmental disruption by nicotine, we examined white matter microstructure in 67 adolescent smokers and nonsmokers with and without prenatal exposure to maternal smoking. The groups did not differ in age, educational attainment, IQ, years of parent education, or symptoms of inattention. Diffusion tensor anisotropy and anatomical magnetic resonance images were acquired, and auditory attention was assessed, in all subjects. Both prenatal exposure and adolescent exposure to tobacco smoke was associated with increased fractional anisotropy (FA) in anterior cortical white matter. Adolescent smoking was also associated with increased FA of regions of the internal capsule that contain auditory thalamocortical and corticofugal fibers. FA of the posterior limb of the left internal capsule was positively correlated with reaction time during performance of an auditory attention task in smokers but not in nonsmokers. Development of anterior cortical and internal capsule fibers may be particularly vulnerable to disruption in cholinergic signaling induced by nicotine in tobacco smoke. Nicotine-induced disruption of the development of auditory corticofugal fibers may interfere with the ability of these fibers to modulate ascending auditory signals, leading to greater noise and reduced efficiency of neurocircuitry that supports auditory processing.

Objective-Abnormalities in the anterior interhemispheric connections provided by the corpus callosum (CC) have long been implicated in bipolar disorder (BD). In this study, we used complementary diffusion tensor imaging (DTI) methods to study the structural integrity of the CC and localization of potential abnormalities in BD. Methods-Subjects included 33 participants with BD and 40 healthy comparison participants.Fractional anisotropy (FA) measures were compared between groups using region of interest (ROI) methods to investigate the anterior, middle and posterior CC and voxel-based methods to further localize abnormalities.Results-In ROI-based analyses, FA was significantly decreased in the anterior and middle CC in the BD group (P<0.05). Voxel-based analyses similarly localized group differences to the genu, rostral body and anterior midbody of CC (P<0.05, corrected).Conclusion-The findings demonstrate abnormalities in the structural integrity of the anterior CC in BD which may contribute to altered inter-hemispheric connectivity in this disorder.The anterior corpus callosum (CC) has been implicated in bipolar disorder (BD) since at least 1903 when Starr described symptoms detected after anterior CC lesions similar to those of BD, such as "undue excitement, causeless laughter, unusual crying, great depression and a lack of harmony between the association of ideas and the state of feeling which they should awaken" (1). An early magnetic resonance imaging (MRI) study of cerebral morphology in BD detected mid-sagittal CC area decreases (2). Subsequent structural MRI studies provided further evidence for CC white matter abnormalities in BD including in volume, signal intensity Corresponding Author: Fei Wang, M.D., Ph.D. Department of Psychiatry, Yale University School of Medicine, Mailing Address: 300 George Street, Suite 901, New Haven, CT 06511, Phone: 203-785-6180, Fax: 203-737-2513, email: fei.wang@yale.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. and structural integrity (3-5), although reports varied in the CC subregions studied and regional differences detected. In this study, complementary diffusion tensor imaging (DTI) region of interest (ROI) and voxel-based methods were used to study the structural integrity of CC white matter in BD and assess the regional localization of differences. Anterior CC reductions in FA in BD were anticipated. Methods ParticipantsThe Structured Clinical Interview for DSM-IV Axis I Disorders Version 2.0 (SCID) (6) confirmed the presence or absence of Axis I Disorders and mood state at scanning for the 33 BD and 40 healt...