These results suggest that patients with glaucoma undergo widespread and complex changes in cortical brain structure and that the extent of these changes correlates with disease severity.

Klinefelter Syndrome (KS) is a genetic disorder characterized by a supernumerary X chromosome. As such, KS offers a naturally occurring human model for the study of both X-chromosome gene expression and androgen on brain development. Previous neuroimaging studies reveal neuroanatomical variations associated with KS, but differ widely with respect to subject inclusion criteria, including mosaicism, pubertal status, and history of testosterone replacement therapy (TRT), all factors likely to influence neurodevelopment. We conducted a voxel-based morphometry (VBM) study of regional grey and white matter volumes in 31 KS males (mean age: 9.69 years ± SD: 1.70) and 36 typically developing (TD) male controls (10.99 ± 1.72). None of the participants with KS had received TRT, and all were prepubertal and had non-mosaic 47, XXY karyotypes. After controlling for age, males with KS showed trends (0.05

Purpose: To develop a practical protocol for diffusion tensor imaging (DTI) of the human optic nerve with echo planar imaging (EPI) geometric distortion correction. Materials and Methods:A conventional DTI protocol was modified to acquire images with fat and cerebrospinal fluid (CSF) suppression and field inhomogeneity maps of contiguous coronal slices covering the whole brain. The technique was applied to healthy volunteers and multiple sclerosis patients with and without a history of unilateral optic neuritis. DTI measures and optic nerve tractography before and after geometric distortion correction were compared. Diffusion measures from left and right or from affected and unaffected eyes in different subject cohorts were reported. Results:The image geometry after correction closely resembled reference anatomical images. Optic nerve tractography became feasible after distortion correction. The diffusion measures from the healthy volunteers were in good agreement with the literature. Statistically significant differences were found in the fractional anisotropy and orthogonal eigenvalues between affected and unaffected eyes in optic neuritis patients with poor recovery. The diffusion measures before and after geometric distortion correction were not significantly different. For cohorts without optic neuritis, the difference between diffusion measures from left and right eyes was not statistically significant. Conclusion:The proposed technique could provide a practical DTI protocol to study the human optic nerve. MAGNETIC RESONANCE DIFFUSION TENSOR IMAG-ING (DTI) (1) has become a well-known clinical research tool to investigate brain tissue microstructure in vivo. DTI provides quantitative measures reflecting the integrity of the axonal fiber tracts in the central nervous system (CNS) via observation of water diffusion anisotropy. This information allows tractography of the fiber bundles suggesting connections between cortical regions. DTI has been applied to study changes associated with neurodevelopmental disorders and changes due to trauma and neurodegenerative diseases (2,3).DTI of the human optic nerve has been explored by many research groups (4 -17). As a pure white matter tract and most of its course being structurally isolated from the rest of the CNS, the optic nerve can serve as a unique structure to study the changes in the CNS due to multiple sclerosis (MS) and optic neuritis (ON). For example, acute inflammation with visual impairment is a first clinical presentation of CNS demyelination. About 20%-30% of patients with this symptom will develop MS and nearly 50% of the MS patients will develop ON (18). With a reliable assessment of visual function and the quantitative measurements from DTI, the impact of injuries and diseases to the optic nerves can be closely studied. However, DTI of the optic nerves is challenging because of their small diameter, confounding signals from surrounding fat tissue and cerebrospinal fluid (CSF), magnetic susceptibility gradients due to adjacent sinuses and bony structu...

We hypothesized that chelating Gd(III) to 1,4,7-tris(carboxymethylaza)cyclododecane-10-azaacetylamide (DO3A) on peptide nucleic acid (PNA) hybridization probes would provide a magnetic resonance genetic imaging agent capable of hybridization to a specific mRNA. Because of the low sensitivity of Gd(III) as an magnetic resonance imaging (MRI) contrast agent, a single Gd-DO3A complex per PNA hybridization agent could not provide enough contrast for detection of cancer gene mRNAs, even at thousands of mRNA copies per cell. To increase the Gd(III) shift intensity of MRI genetic imaging agents, we extended a novel DO3An-polydiamidopropanoyl (PDAPm) dendrimer, up to n = 16, from the N-terminus of KRAS PNA hybridization agents by solid phase synthesis. A C-terminal d(Cys-Ser-Lys-Cys) cyclized peptide analog of insulin-like growth factor 1 (IGF1) was included to enable receptor-mediated cellular uptake. Molecular dynamic simulation of the (Gd-DO3A-AEEA)16-PDAP4-AEEA2-KRAS PNA-AEEA-d(Cys-Ser-Lys-Cys) genetic imaging nanoparticles in explicit water yielded a pair correlation function similar to that of PAMAM dendrimers, and a predicted structure in which the PDAP dendron did not sequester the PNA. Thermal melting measurements indicated that the size of the PDAP dendron included in the (DO3A-AEEA)n-PDAPm-AEEA2-KRAS PNA-AEEA-d(Cys-Ser-Lys-Cys) probes (up to 16 Gd(III) cations per PNA) did not depress the melting temperatures (Tm) of the complementary PNA/RNA hybrid duplexes. The Gd(III) dendrimer PNA genetic imaging agents in phantom solutions displayed significantly greater T1 relaxivity per probe (r1 = 30.64 ± 2.68 mM-1 s-1 for n = 2, r1 = 153.84 ± 11.28 mM-1 s-1 for n = 8) than Gd-DTPA (r1 = 10.35 ± 0.37 mM-1 s-1), but less than that of (Gd-DO3A)32-PAMAM dendrimer (r1 = 771.84 ± 20.48 mM-1 s-1) (P < 0.05). Higher generations of PDAP dendrimers with 32 or more Gd-DO3A residues attached to PNA-d(Cys-Ser-Lys-Cys) genetic imaging agents might provide greater contrast for more sensitive detection.

AIM To assess global and regional brain matter variations associated with XYY syndrome by comparison with Klinefelter syndrome and typical development. METHOD We used two conceptually distinct voxel-based magnetic resonance imaging methods to examine brain structure in young males with XYY syndrome: (1) volumetric comparison to assess global grey and white matter volumes and (2) support vector machine-based multivariate pattern classification analysis to assess regional neuroanatomy. We assessed verbal, non-verbal, and spatial abilities with the Differential Ability Scales (DAS), and we measured autism diagnostic criteria in eight males with XYY syndrome using the Social Responsiveness Scale and the Autism Diagnostic Interview-Revised (ADI-R). RESULTS A comparison of 36 typically developing males (mean age 11y, SD 1y 9mo), 31 males with Klinefelter syndrome (mean age 9y 8mo, SD 1y 8mo), and eight males with XYY syndrome (mean age 11y 6mo, SD 1y 11mo) showed that total white and grey matter volumes were significantly, or nearly significantly, higher in males with XYY syndrome than in males belonging to the other two groups (grey matter: XYY males vs typically developing males, p<0.006; XYY vs males with Klinefelter syndrome, p<0.001; white matter: XYY males vs typically developing males, p=0.061; XYY males vs males with Klinefelter syndrome, p=0.004). Voxel-based multivariate pattern classification analysis indicates that, after controlling for global volumes, regional brain variations in XYY syndrome are more like those found in Klinefelter syndrome than those occurring in typical development. Further, visualization of classification parameters suggests that insular and frontotemporal grey matter and white matter, including known language areas, are reduced in males with XYY syndrome, similar to what is seen in Klinefelter syndrome. In males with XYY syndrome, DAS verbal and non-verbal scores were significantly lower than in typically developing participants (both p<0.001). DAS scores were not significantly different between XYY and Klinefelter syndrome groups. In five of eight males with XYY syndrome, the Social Responsiveness Scale score exceeded the cut-off for a likely diagnosis of autism spectrum disorder (ASD). In three of eight males with XYY syndrome, the ADI-R score met the cut-off for ASD diagnosis; in another two, ADI-R scores within the social and communication domains met the cut-off values for a diagnosis of ASD. INTERPRETATION The results suggest that genetic variations associated with XYY syndrome result in increased brain matter volumes, a finding putatively related to the increased frequency of ASDs in individuals with this condition. In addition, frontotemporal grey and white matter reductions in XYY syndrome provide a likely neuroanatomical correlate for observed language impairments.