Assessment of liver cirrhosis for patients with Child's A classification before hepatectomy using dynamic contrast-enhanced MRI.

AIM: To determine the feasibility of semi-quantitative haemodynamic parameters derived from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to assess liver fibrosis. MATERIALS AND METHODS: Seventy-five patients with Child's A classification (males/females=24/51; average age, 58 years; range, 30-80 years) received DCE-MRI 3 days prior to hepatectomy. Semi-quantitative haemodynamic parameters, including the wash-in slope, wash-out slope, and time-to-peak, were calculated from DCE-MRI data. Liver fibrosis of the resected non-tumour liver was graded pathologically from F0 (no fibrosis) to F6 (cirrhosis) in the regions corresponding to those assessed by DCE-MRI. RESULTS: The wash-out slope showed higher interobserver and intra-observer reliabilities than the wash-in slope and time-to-peak. There was a significant positive correlation between the wash-out slope and pathological grade of fibrosis (Spearman's correlation coefficient: r=0.5331, p<0.0001). The area under the receiver operating characteristic curve was 0.8066 when using the wash-out slope to differentiate cirrhosis (grade F6) from non-cirrhosis (grades F0-5). Using the cut-off point that maximised specificity, the sensitivity was 62.07%, specificity was 91.30%, positive predictive value was 81.81%, negative predictive value was 79.25%, and accuracy was 80%. CONCLUSIONS: The wash-out slope derived from DCE-MRI might be potentially useful in assessing liver cirrhosis in patients with Child's A classification before hepatectomy.

Hippocampal Atrophy Is Associated with Altered Hippocampus-Posterior Cingulate Cortex Connectivity in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

BACKGROUND AND PURPOSE: Unilateral mesial temporal lobe epilepsy and hippocampal sclerosis have structural and functional abnormalities in the mesial temporal regions. To gain insight into the pathophysiology of the epileptic network in mesial temporal lobe epilepsy with hippocampal sclerosis, we aimed to clarify the relationships between hippocampal atrophy and the altered connection between the hippocampus and the posterior cingulate cortex in patients with mesial temporal lobe epilepsy with hippocampal sclerosis. MATERIALS AND METHODS: Fifteen patients with left mesial temporal lobe epilepsy with hippocampal sclerosis and 15 healthy controls were included in the study. Multicontrast MR imaging, including high-resolution T1WI, diffusion spectrum imaging, and resting-state fMRI, was performed to measure the hippocampal volume, structural connectivity of the inferior cingulum bundle, and intrinsic functional connectivity between the hippocampus and the posterior cingulate cortex, respectively. RESULTS: Compared with controls, patients had decreased left hippocampal volume (volume ratio of the hippocampus and controls, 0.366% ± 0.029%; patients, 0.277% ± 0.063%, corrected P = .002), structural connectivity of the bilateral inferior cingulum bundle (generalized fractional anisotropy, left: controls, 0.234 ± 0.020; patients, 0.193 ± 0.022, corrected P = .0001, right: controls, 0.226 ± 0.022; patients, 0.208 ± 0.017, corrected P = .047), and intrinsic functional connectivity between the left hippocampus and the left posterior cingulate cortex (averaged z-value: controls, 0.314 ± 0.152; patients, 0.166 ± 0.062). The left hippocampal volume correlated with structural connectivity positively (standardized ß = 0.864, P = .001), but it had little correlation with intrinsic functional connectivity (standardized ß = -0.329, P = .113). On the contralesional side, the hippocampal volume did not show any significant correlation with structural connectivity or intrinsic functional connectivity (F2,12 = 0.284, P = .757, R2 = 0.045). CONCLUSIONS: In left mesial temporal lobe epilepsy with hippocampal sclerosis, the left inferior cingulum bundle undergoes degeneration in tandem with the left hippocampal volume, whereas intrinsic functional connectivity seems to react by compensating the loss of connectivity. Such insight might be helpful in understanding the development of the epileptic network in left mesial temporal lobe epilepsy with hippocampal sclerosis.

Shared atypical brain anatomy and intrinsic functional architecture in male youth with autism spectrum disorder and their unaffected brothers.

BACKGROUND: Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder, yet the search for definite genetic etiologies remains elusive. Delineating ASD endophenotypes can boost the statistical power to identify the genetic etiologies and pathophysiology of ASD. We aimed to test for endophenotypes of neuroanatomy and associated intrinsic functional connectivity (iFC) via contrasting male youth with ASD, their unaffected brothers and typically developing (TD) males. METHOD: The 94 participants (aged 9-19 years) - 20 male youth with ASD, 20 unaffected brothers and 54 TD males - received clinical assessments, and undertook structural and resting-state functional magnetic resonance imaging scans. Voxel-based morphometry was performed to obtain regional gray and white matter volumes. A seed-based approach, with seeds defined by the regions demonstrating atypical neuroanatomy shared by youth with ASD and unaffected brothers, was implemented to derive iFC. General linear models were used to compare brain structures and iFC among the three groups. Assessment of familiality was investigated by permutation tests for variance of the within-family pair difference. RESULTS: We found that atypical gray matter volume in the mid-cingulate cortex was shared between male youth with ASD and their unaffected brothers as compared with TD males. Moreover, reduced iFC between the mid-cingulate cortex and the right inferior frontal gyrus, and increased iFC between the mid-cingulate cortex and bilateral middle occipital gyrus were the shared features of male ASD youth and unaffected brothers. CONCLUSIONS: Atypical neuroanatomy and iFC surrounding the mid-cingulate cortex may be a potential endophenotypic marker for ASD in males.

Different neural substrates for executive functions in youths with ADHD: a diffusion spectrum imaging tractography study.

BACKGROUND: The relationship between white-matter tracts and executive functions (EF) in attention deficit hyperactivity disorder (ADHD) has not been well studied and previous studies mainly focused on frontostriatal (FS) tracts. The authors explored the microstructural property of several fibre tracts hypothesized to be involved in EF, to correlate their microstructural property with EF, and to explore whether such associations differ between ADHD and typically developing (TD) youths. METHOD: We assessed 45 youths with ADHD and 45 individually matched TD youths with a computerized test battery for multiple dimensions of EF. From magnetic resonance imaging, FS tract, superior longitudinal fasciculus (SLF), arcuate fasciculus (AF) and cingulum bundle (CB) were reconstructed by diffusion spectrum imaging tractography. The generalized fractional anisotropy (GFA) values of white-matter tracts were computed to present microstructural property of each tract. RESULTS: We found lower GFA in the left FS tract, left SLF, left AF and right CB, and poorer performance in set-shifting, sustained attention, cognitive inhibition and visuospatial planning in ADHD than TD. The ADHD and TD groups demonstrated different association patterns between EF and fibre tract microstructural property. Most of the EF were associated with microstructural integrity of the FS tract and CB in TD youths, while with that of the FS tract, SLF and AF in youths with ADHD. CONCLUSIONS: Our findings support that the SLF, AF and CB also involve in a wide range of EF and that the main fibre tracts involved in EF are different in youths with ADHD.

Association between microstructural integrity of frontostriatal tracts and school functioning: ADHD symptoms and executive function as mediators.

BACKGROUND: Deficits in executive function (EF), impaired school functioning and altered white matter integrity in frontostriatal networks have been associated with attention-deficit/hyperactivity disorder (ADHD). However, relationships between impairments in these areas are unclear. Using a sample of youths with and without ADHD, this study examined the association between microstructural integrity of frontostriatal tracts and school dysfunction and the mediating roles of EF and ADHD symptoms in this association. METHOD: The sample included 32 Taiwanese youths with ADHD and 32 age-, sex-, handedness- and IQ-matched typically-developing (TD) youths. Participants were assessed using psychiatric interviews, parent reports on ADHD symptoms and school functioning, and EF measures from the Cambridge Neuropsychological Test Automated Battery (CANTAB). The frontostriatal tracts were reconstructed by diffusion spectrum imaging (DSI) tractography and were subdivided into four functionally distinct segments: caudate-dorsolateral, caudate-medial prefrontal, caudate-orbitofrontal and caudate-ventrolateral tracts. RESULTS: Youths with ADHD, relative to TD youths, showed altered white matter integrity in all four bilateral pairs of frontostriatal tracts (decreased general fractional anisotropy, GFA), had poor attention, vigilance and response inhibition, and showed impaired school functioning. Altered microstructural integrity in frontostriatal tracts was significantly associated with school dysfunction, which was mediated by EF measures of attention/vigilance and response inhibition in addition to inattention and hyperactivity symptoms. CONCLUSIONS: Our findings demonstrate an association between white matter integrity in the frontostriatal networks and school functioning and suggest that EF deficits and ADHD symptoms may be the mediating mechanisms for this association. Future research is needed to test the directionality and specificity of this finding.

Neural substrates of behavioral variability in attention deficit hyperactivity disorder: based on ex-Gaussian reaction time distribution and diffusion spectrum imaging tractography.

BACKGROUND: Increased intra-individual variability (IIV) in reaction time (RT) across various tasks is one ubiquitous neuropsychological finding in attention deficit hyperactivity disorder (ADHD). However, neurobiological underpinnings of IIV in individuals with ADHD have not yet been fully delineated. The ex-Gaussian distribution has been proved to capture IIV in RT. The authors explored the three parameters [µ (mu), σ (sigma), τ (tau)] of an ex-Gaussian RT distribution derived from the Conners' continuous performance test (CCPT) and their correlations with the microstructural integrity of the frontostriatal-caudate tracts and the cingulum bundles. METHOD: We assessed 28 youths with ADHD (8-17 years; 25 males) and 28 age-, sex-, IQ- and handedness-matched typically developing (TD) youths using the CCPT, Wechsler Intelligence Scale for Children, 3rd edition and magnetic resonance imaging (MRI). Microstructural integrity, indexed by generalized fractional anisotropy (GFA), was measured by diffusion spectrum imaging tractrography on a 3-T MRI system. RESULTS: Youths with ADHD had larger σ (s.d. of Gaussian distribution) and τ (mean of exponential distribution) and reduced GFA in four bilateral frontostriatal tracts. With increased inter-stimulus intervals of CCPT, the magnitude of greater τ in ADHD than TD increased. In ADHD youths, the cingulum bundles and frontostriatal integrity were associated with three ex-Gaussian parameters and with µ (mean of Gaussian distribution) and τ, respectively; while only frontostriatal GFA was associated with µ and τ in TD youths. CONCLUSIONS: Our findings suggest the crucial role of the integrity of the cingulum bundles in accounting for IIV in ADHD. Involvement of different brain systems in mediating IIV may relate to a distinctive pathophysiological processing and/or adaptive compensatory mechanism.

Microstructural integrity of cerebral fiber tracts in hereditary spastic paraparesis with SPG11 mutation.

BACKGROUND AND PURPOSE: ARHSP-TCC is characterized by progressive leg spasticity, ataxia, and cognitive dysfunction. Although mutations in the human SPG11 gene were identified as responsible for ARHSP-TCC, the cerebral fiber integrity has not been assessed systemically. The objective of this study was to assess cerebral fiber integrity and its clinical significance in patients with ARHSP-TCC. MATERIALS AND METHODS: Five patients from 2 families who were clinically and genetically confirmed to have ARHSP-TCC were examined by neuropsychological evaluation and DSI of the brain. We performed voxel-based GFA analysis for global white matter evaluation, tractography-based analysis for tract-to-tract comparisons, and tract-specific analysis of the CST to evaluate microstructural integrity along the axonal direction. RESULTS: The neuropsychological evaluation revealed widespread cognitive decline across all domains. Voxel-based analysis showed global reduction of GFA in the cerebral white matter. Tractography-based analysis revealed a significant reduction of the microstructural integrity in all neural fiber types, while commissure and association fibers had more GFA reduction than projection fibers (P < .00001). Prefrontal and motor portions of the CC were most severely affected among all fiber tracts (P < .00001, P = .018). Tract-specific analysis of the CST validated a "dying-back" phenomenon (R(2) = 0.68, P < .00001). CONCLUSIONS: There was a characteristic gradation in the reduction of microstructural integrity among fiber types and within the CC in patients with the SPG11 mutation. The dying-back process in CST might explain the pathogenic mechanisms for ARHSP-TCC.

Tract-specific and region of interest analysis of corticospinal tract integrity in subcortical ischemic stroke: reliability and correlation with motor function of affected lower extremity.

BACKGROUND AND PURPOSE: TS analysis has been suggested as a useful method to evaluate the fiber integrity of white matter tracts. This study investigated the intrarater and interrater reliability and validity of a TS analysis for the CST and compared the results with those of a ROI-based analysis. MATERIALS AND METHODS: Diffusion spectrum imaging was performed on 7 patients with subcortical ischemic stroke on a 3T MR imaging system. For the TS analysis, seed regions were placed at the cerebral peduncle and the medial portion of the primary motor cortex to reconstruct the tracts of the CST for motor control of the lower extremity. The mean GFA was measured at the PLIC by calculating the weighted sum of the GFAs sampled by the CST tracts at this segment. For the ROI-based analysis, the posterior two-thirds of the PLIC were enclosed on the GFA maps, and the mean GFA in this ROI was calculated. RESULTS: The results showed good-to-excellent intrarater and interrater reliability on the seed region/ROI placement (mean kappa values >0.80) and mean GFA values (ICCs >0.90) for both the TS and ROI-based analyses. Both the GFA(PLIC-TS) and GFA(PLIC-ROI) values were highly correlated with the motor function of the affected lower extremity (r = 0.76 and 0.80, respectively; P < .05). CONCLUSIONS: We demonstrated good reliability and validity of the TS and ROI-based analyses of the CST corresponding to lower extremity motor control in patients with subcortical ischemic stroke.

Effect of cardiac rehabilitation on angiogenic cytokines in postinfarction patients.

OBJECTIVE: To determine whether cardiac rehabilitation influences plasma levels of angiogenic cytokines and their correlation with myocardial blood flow (MBF). DESIGN: Randomised controlled study. SETTING: Tertiary cardiac centre. PATIENTS: 39 postinfarction patients randomised to either a 3-month training group (n = 20) or a non-training group (n = 19), and 19 normal controls. INTERVENTIONS: Cardiac rehabilitation. MAIN OUTCOME MEASURES: MBF by cardiac magnetic resonance imaging, and plasma levels of stem cell factor (SCF), stromal-derived factor-1 (SDF-1), and vascular endothelial growth factor (VEGF) measured at enrolment and at 3 months after randomisation. RESULTS: At baseline, when compared with the healthy subjects, postinfarction patients had a lower MBF in the infarcted myocardium during dipyridamole-induced stress (1.65 (0.58) vs 2.77 (0.78) ml/min/g, p<0.001) but higher plasma levels of VEGF (3.65 (0.75) vs 2.77 (0.59) pg/ml, p<0.001 expressed as the natural logarithm) and SDF-1 (2113 (345) vs 1869 (309) pg/ml, p = 0.009). Only SDF-1 was inversely associated with stress MBF in both remote (r = -0.39, p = 0.03) and infarcted myocardium (r = -0.62, p<0.001). After 3 months, the training group's stress MBF had increased by 33% in the remote (p<0.001) and 28% in infarcted myocardium (p = 0.02), while VEGF decreased by 9% (p = 0.01), and SDF-1 decreased by 11% (p = 0.02). The change in SDF-1 was inversely correlated with the change in stress MBF in both remote (r = -0.40, p = 0.01) and infarcted myocardium (r = -0.50, p = 0.001). In the non-training group, MBF and cytokines were unchanged. CONCLUSION: Cardiac rehabilitation improves stress MBF in postinfarction patients, with an inverse decrease in circulating angiogenic cytokines.

Diffusion spectrum magnetic resonance imaging (DSI) tractography of crossing fibers.

MRI tractography is the mapping of neural fiber pathways based on diffusion MRI of tissue diffusion anisotropy. Tractography based on diffusion tensor imaging (DTI) cannot directly image multiple fiber orientations within a single voxel. To address this limitation, diffusion spectrum MRI (DSI) and related methods were developed to image complex distributions of intravoxel fiber orientation. Here we demonstrate that tractography based on DSI has the capacity to image crossing fibers in neural tissue. DSI was performed in formalin-fixed brains of adult macaque and in the brains of healthy human subjects. Fiber tract solutions were constructed by a streamline procedure, following directions of maximum diffusion at every point, and analyzed in an interactive visualization environment (TrackVis). We report that DSI tractography accurately shows the known anatomic fiber crossings in optic chiasm, centrum semiovale, and brainstem; fiber intersections in gray matter, including cerebellar folia and the caudate nucleus; and radial fiber architecture in cerebral cortex. In contrast, none of these examples of fiber crossing and complex structure was identified by DTI analysis of the same data sets. These findings indicate that DSI tractography is able to image crossing fibers in neural tissue, an essential step toward non-invasive imaging of connectional neuroanatomy.

The impact of lesion length on angiographic restenosis after vertebral artery origin stenting.

OBJECTIVE: To evaluate the effect of lesion length on in-stent restenosis (ISR) of vertebral artery (VA) origin stenting. METHODS: We retrospectively analyzed the medical and radiological records of patients receiving VA origin stenting from March 1999 to June 2005. They were subdivided according to lesion length. ISR was defined as >50% diameter narrowing in stent. RESULTS: Eighty symptomatic patients (64 male, mean age 72 years) with 90 lesions treated with balloon expandable tubular coronary stents were enrolled. There were 34 patients with 38 short lesions (length5 mm, <10 mm, group 2) and 9 patients with 10 long lesions (length>or=10 mm, group 3). Eighty seven bare-metal stents and 3 drug-eluting stents were implanted. Repeat angiography was done in 40 lesions (44%) at 11.7+/-9.6 months. The ISR rate in group 1, 2, 3 is 21%, 29%, and 50% (p=0.486). Multivariable Cox regression analysis showed lesion length was the only significant independent predictor of ISR (hazard ratio: 1.19, p=0.039). CONCLUSION: ISR of VA origin stenting is common. Lesion length is an important predictor of ISR in VA origin stenting.