Background: Normal aging is accompanied by a decline of cognitive abilities, and executive skills may be affected selectively, but the underlying mechanisms remain obscure and preventive strategies are lacking. It has been suggested that cortical “disconnection” due to the loss of white matter fibers may play an important role. But, to date, there has been no direct demonstration of structural disconnection in humans in vivo. Methods: The authors used diffusion tensor MRI to look for evidence of ultrastructural changes in cerebral white matter in a group of 20 elderly volunteers with normal conventional MRI scans, and a group of 10 younger controls. The older group also underwent neuropsychological assessment. Results: Diffusional anisotropy, a marker of white matter tract integrity, was reduced in the white matter of older subjects and fell linearly with increasing age in the older group. Mean diffusivity was higher in the older group and increased with age. These changes were maximal in anterior white matter. In the older group, anterior mean diffusivity correlated with executive function assessed by the Trail Making Test. Conclusions: These findings provide direct evidence that white matter tract disruption occurs in normal aging and would be consistent with the cortical disconnection hypothesis of age-related cognitive decline. Maximal changes in anterior white matter provide a plausible structural basis for selective loss of executive functions. In addition to providing new information about the biological basis of cognitive abilities, diffusion tensor MRI may be a sensitive tool for assessing interventions aimed at preventing cognitive decline.

Background and Purpose— Because the long-term security of endovascular treatments remains uncertain, a follow-up study of the patients treated in the International Subarachnoid Aneurysm Trial was performed to compare the frequency, timing, and consequences of aneurysm recurrence. Methods— Patient data were reclassified by actual treatment performed. Aneurysm and patient characteristics, including occlusion grades, time and type of retreatment, and clinical outcomes, were compared. The relationship between these variables and late retreatment as a surrogate for recurrence was analyzed by means of the Cox proportional hazards model. Results— Retreatment was performed in 191 of 1096 (17.4%) patients after primary endovascular coiling (EVT) and in 39 of 1012 patients (3.8%) after neurosurgical clipping. After EVT, 97 (8.8%) patients were retreated early and 94 (9.0%) late, 7 (0.6%) after rebleeding and 87 (8.3%) without. The mean time to late retreatment was 20.7 months. After neurosurgical clipping, 30 (2.9%) patients were retreated early and 9 (0.85%) late, 3 (0.3%) after rebleeding and 6 (0.6%) without. The mean time to late retreatment was 5.7 months. The hazard ratio (HR) for retreatment after EVT was 6.9 (95% CI=3.4 to 14.1) after adjustment for age ( P =0.001, HR=0.97, 95% CI=0.95 to 0.98), lumen size ( P =0.006, HR=1.1, 95% CI=1.03 to 1.18), and incomplete occlusion ( P <0.001, HR=7.6, 95% CI=3.3 to 17.5). Conclusions— Late retreatment was 6.9 times more likely after EVT. Younger age, larger lumen size, and incomplete occlusion were risk factors for late retreatment after EVT. After neurosurgical clipping, retreatments were earlier; whereas EVT retreatments continued to be performed throughout the follow-up period. Short-term follow-up imaging is therefore insufficient to detect recurrences after EVT.

A first-ever spinal cord imaging meeting was sponsored by the International Spinal Research Trust and the Wings for Life Foundation with the aim of identifying the current state-of-the-art of spinal cord imaging, the current greatest challenges, and greatest needs for future development. This meeting was attended by a small group of invited experts spanning all aspects of spinal cord imaging from basic research to clinical practice. The greatest current challenges for spinal cord imaging were identified as arising from the imaging environment itself; difficult imaging environment created by the bone surrounding the spinal canal, physiological motion of the cord and adjacent tissues, and small cross-sectional dimensions of the spinal cord, exacerbated by metallic implants often present in injured patients. Challenges were also identified as a result of a lack of "critical mass" of researchers taking on the development of spinal cord imaging, affecting both the rate of progress in the field, and the demand for equipment and software to manufacturers to produce the necessary tools. Here we define the current state-of-the-art of spinal cord imaging, discuss the underlying theory and challenges, and present the evidence for the current and potential power of these methods. In two review papers (part I and part II), we propose that the challenges can be overcome with advances in methods, improving availability and effectiveness of methods, and linking existing researchers to create the necessary scientific and clinical network to advance the rate of progress and impact of the research.

Background: Ischemic leukoaraiosis (ILA) refers to diffuse T2-weighted white matter hyperintensity in the context of a previous clinical lacunar stroke. Reduced cerebral blood flow (CBF) in white matter has been demonstrated, but it is not known whether hypoperfusion is confined to lesions or extends into normal-appearing white matter. Demonstrating changes in normal-appearing white matter would provide clues to the importance of hypoperfusion in pathogenesis and would be an obvious target for therapies aimed at restoring white matter blood flow. Methods: Twenty-one patients with ILA, and 16 age-matched control subjects, underwent exogenous contrast-based quantitative perfusion MRI. CBF was determined both within and outside areas of T2-weighted hyperintensity in both periventricular white matter and the centrum semiovale. Results: CBF of normal-appearing white matter was reduced in periventricular regions (for patients with ILA, 17.9 ± 5.6 mL/100 g/min; for controls, 21.6 ± 5.1 mL/100 g/min; p = 0.046). CBF in gray matter and normal-appearing white matter of the centrum semiovale did not differ significantly between groups. In normal-appearing white matter in patients, CBF was higher in the centrum semiovale than periventricular white matter, with a similar trend in control subjects. Conclusions: Hypoperfusion may be an early feature in the development of periventricular lesions in ILA and may play a direct pathogenic role. Serial studies are now needed to determine whether these changes herald the appearance of new lesions and represent ‘at risk’ white matter, and to determine whether pharmacological agents can restore perfusion of normal-appearing white matter.

We present the use of an entropy focus criterion to enable automatic focusing of motion corrupted magnetic resonance images. We demonstrate the principle using illustrative examples from cooperative volunteers. Our technique can determine unknown patient motion or use knowledge of motion from other measures as a starting estimate. The motion estimate is used to compensate the acquired data and is iteratively refined using the image entropy. Entropy focuses the whole image principally by favoring the removal of motion induced ghosts and blurring from otherwise dark regions of the image. Using only the image data, and no special hardware or pulse sequences, we demonstrate correction for arbitrary rigid-body translational motion in the imaging plane and for a single rotation. Extension to three-dimensional (3-D) and more general motion should be possible. The algorithm is able to determine volunteer motion well. The mean absolute deviation between algorithm and navigator-echo-determined motion is comparable to the displacement step size used in the algorithm. Local deviations from the recorded motion or navigator-determined motion are explained and we indicate how enhanced focus criteria may be derived. In all cases we were able to compensate images for patient motion, reducing blurring and ghosting.

Murat Gunel and colleagues report a genome-wide association study for intracranial aneurysm and identify risk variants near RBBP8, CNNM and STARD13. Saccular intracranial aneurysms are balloon-like dilations of the intracranial arterial wall; their hemorrhage commonly results in severe neurologic impairment and death. We report a second genome-wide association study with discovery and replication cohorts from Europe and Japan comprising 5,891 cases and 14,181 controls with ∼832,000 genotyped and imputed SNPs across discovery cohorts. We identified three new loci showing strong evidence for association with intracranial aneurysms in the combined dataset, including intervals near RBBP8 on 18q11.2 (odds ratio (OR) = 1.22, P = 1.1 × 10−12), STARD13-KL on 13q13.1 (OR = 1.20, P = 2.5 × 10−9) and a gene-rich region on 10q24.32 (OR = 1.29, P = 1.2 × 10−9). We also confirmed prior associations near SOX17 (8q11.23–q12.1; OR = 1.28, P = 1.3 × 10−12) and CDKN2A-CDKN2B (9p21.3; OR = 1.31, P = 1.5 × 10−22). It is noteworthy that several putative risk genes play a role in cell-cycle progression, potentially affecting the proliferation and senescence of progenitor-cell populations that are responsible for vascular formation and repair.