Prenatal exposure to maternal cigarette smoking and structural properties of the human corpus callosum.

Alterations induced by prenatal exposure to nicotine have been observed in experimental (rodent) studies. While numerous developmental outcomes have been associated with prenatal exposure to maternal cigarette smoking (PEMCS) in humans, the possible relation with brain structure is less clear. Here we sought to elucidate the relation between PEMCS and structural properties of human corpus callosum in adolescence and early adulthood in a total of 1,747 youth. We deployed three community-based cohorts of 446 (age 25-27 years, 46% exposed), 934 (age 12-18 years, 47% exposed) and 367 individuals (age 18-21 years, 9% exposed). A mega-analysis revealed lower mean diffusivity in the callosal segments of exposed males. We speculate that prenatal exposure to maternal cigarette smoking disrupts the early programming of callosal structure and increases the relative portion of small-diameter fibres.

Structural properties of the human corpus callosum: Multimodal assessment and sex differences.

A number of structural properties of white matter can be assessed in vivo using multimodal magnetic resonance imaging (MRI). We measured profiles of R1 and R2 relaxation rates, myelin water fraction (MWF) and diffusion tensor measures (fractional anisotropy [FA], mean diffusivity [MD]) across the mid-sagittal section of the corpus callosum in two samples of young individuals. In Part 1, we compared histology-derived axon diameter (Aboitiz et al., 1992) to MRI measures obtained in 402 young men (19.55 ± 0.84 years) recruited from the Avon Longitudinal Study on Parents and Children. In Part 2, we examined sex differences in FA, MD and magnetization transfer ratio (MTR) across the corpus callosum in 433 young (26.50 ± 0.51 years) men and women recruited from the Northern Finland Birth Cohort 1986. We found that R1, R2, and MWF follow the anterior-to-posterior profile of small-axon density. Sex differences in mean MTR were similar across the corpus callosum (males > females) while these in FA differed by the callosal segment (Body: M>F; Splenium: F>M). We suggest that the values of R1, R2 and MWF are driven by high surface area of myelin in regions with high density of "small axons".

Dual-temporal resolution dynamic contrast-enhanced MRI protocol for blood-brain barrier permeability measurement in enhancing multiple sclerosis lesions.

PURPOSE: To design a more accurate and reproducible technique for the measurement of blood-brain barrier (BBB) permeability in gadolinium-enhancing multiple sclerosis (MS) lesions. MATERIALS AND METHODS: Four MS patients were scanned using a new dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) protocol based on an uninterrupted two-part acquisition consisting of an initial part at high temporal and low spatial resolutions and a second part at low temporal and high spatial resolutions. The method preserves both the high spatial resolution needed for the often small size of lesions and the high temporal resolution required during the first minute after injection to sufficiently sample the first-pass bolus. Simulations compared the performance of this new protocol with the conventional one at low temporal and high spatial resolutions throughout. RESULTS: The BBB permeability estimates changed by up to 33% between the two protocols. The new protocol led to simulated error on K(trans) of 7%-10%, versus 7%-30% with the conventional protocol, and was more robust with respect to offsets between acquisition and injection start times, differences in shape of the first-pass peak, and permeability values. CONCLUSION: The dual-temporal resolution protocol produces improved BBB permeability estimates and provides a more complete view of active inflammatory MS lesion pathology.

Sexual dimorphism in the adolescent brain: Role of testosterone and androgen receptor in global and local volumes of grey and white matter.

Here we examined sex differences in the volumes of grey and white matter, and in grey-matter "density," in a group of typically developing adolescents participating in the Saguenay Youth Study (n=419; 12-18 years). In male adolescents, we also investigated the role of a functional polymorphism in androgen-receptor gene (AR) in moderating the effect of testosterone on volumes of grey and white matter and grey-matter density. Overall, both absolute and relative volumes of white matter were larger in male vs. females adolescents. The relative grey-matter volumes were slightly larger in female than male adolescents and so was the grey-matter density in a large number of cortical regions. In male adolescents, functional polymorphism of AR moderated the effect of testosterone on relative white- and grey-matter volumes. Following a discussion of several methodological and interpretational issues, we outline future directions in investigating brain-behavior relationships vis-à-vis psychopathology.

Sex differences in the growth of white matter during adolescence.

The purpose of this study was to examine sex differences in the maturation of white matter during adolescence (12 to 18 years of age). We measured lobular volumes of white matter and white-matter "density" throughout the brain using T1-weighted images, and estimated the myelination index using magnetisation-transfer ratio (MTR). In male adolescents, we observed age-related increases in white-matter lobular volumes accompanied by decreases in the lobular values of white-matter MTR. White-matter density in the putative cortico-spinal tract (pCST) decreased with age. In female adolescents, on the other hand, we found only small age-related increase in white-matter volumes and no age-related changes in white-matter MTR, with the exception of the frontal lobe where MTR increased. White-matter density in the pCST also increased with age. These results suggest that sex-specific mechanisms may underlie the growth of white matter during adolescence. We speculate that these mechanisms involve primarily age-related increases in axonal calibre in males and increased myelination in females.

Mathematical methods for diffusion MRI processing.

In this article, we review recent mathematical models and computational methods for the processing of diffusion Magnetic Resonance Images, including state-of-the-art reconstruction of diffusion models, cerebral white matter connectivity analysis, and segmentation techniques. We focus on Diffusion Tensor Images (DTI) and Q-Ball Images (QBI).

Information content of SNR/resolution trade-offs in three-dimensional magnetic resonance imaging.

In MRI, a trade-off exists between resolution and signal-to-noise ratio, since different fractions of the available scan time can be used to acquire data at higher spatial frequencies and to perform signal averaging. By comparing a wide variety of 3D isotropic MR scans with different combinations of SNR, resolution, and scan duration, the impact of this trade-off on the image information content was assessed. The information content of mouse brain, mouse whole-body, and human brain images was evaluated using a simple numerical approach, which sums the information contribution of each individual k-space data point. Results show that, with a fixed receiver bandwidth and field of view, the information content of trade-off images is always maximized when the SNR is equal to about 16. The optimal imaging resolution is dependent on the scan duration, as well as certain MR system properties, such as field strength and coil sensitivity. These properties are, however, easily accounted for with the acquisition of a single scout MR image, and the optimal imaging resolution can then be calculated using a simple mathematical relationship. If the imaging task is approached with a predetermined resolution requirement, the same scout scan can be used to calculate the scan duration that will provide the maximum possible information. Using these relationships to maximize the image information content is an excellent technique for guiding the initial selection of imaging parameters.

Increased Extra-axial Cerebrospinal Fluid in High-Risk Infants Who Later Develop Autism.

BACKGROUND: We previously reported that infants who developed autism spectrum disorder (ASD) had increased cerebrospinal fluid (CSF) in the subarachnoid space (i.e., extra-axial CSF) from 6 to 24 months of age. We attempted to confirm and extend this finding in a larger independent sample. METHODS: A longitudinal magnetic resonance imaging study of infants at risk for ASD was carried out on 343 infants, who underwent neuroimaging at 6, 12, and 24 months. Of these infants, 221 were at high risk for ASD because of an older sibling with ASD, and 122 were at low risk with no family history of ASD. A total of 47 infants were diagnosed with ASD at 24 months and were compared with 174 high-risk and 122 low-risk infants without ASD. RESULTS: Infants who developed ASD had significantly greater extra-axial CSF volume at 6 months compared with both comparison groups without ASD (18% greater than high-risk infants without ASD; Cohen's d = 0.54). Extra-axial CSF volume remained elevated through 24 months (d = 0.46). Infants with more severe autism symptoms had an even greater volume of extra-axial CSF from 6 to 24 months (24% greater at 6 months, d = 0.70; 15% greater at 24 months, d = 0.70). Extra-axial CSF volume at 6 months predicted which high-risk infants would be diagnosed with ASD at 24 months with an overall accuracy of 69% and corresponding 66% sensitivity and 68% specificity, which was fully cross-validated in a separate sample. CONCLUSIONS: This study confirms and extends previous findings that increased extra-axial CSF is detectable at 6 months in high-risk infants who develop ASD. Future studies will address whether this anomaly is a contributing factor to the etiology of ASD or an early risk marker for ASD.

Saguenay Youth Study: a multi-generational approach to studying virtual trajectories of the brain and cardio-metabolic health.

This paper provides an overview of the Saguenay Youth Study (SYS) and its parental arm. The overarching goal of this effort is to develop trans-generational models of developmental cascades contributing to the emergence of common chronic disorders, such as depression, addictions, dementia and cardio-metabolic diseases. Over the past 10 years, we have acquired detailed brain and cardio-metabolic phenotypes, and genome-wide genotypes, in 1029 adolescents recruited in a population with a known genetic founder effect. At present, we are extending this dataset to acquire comparable phenotypes and genotypes in the biological parents of these individuals. After providing conceptual background for this work (transactions across time, systems and organs), we describe briefly the tools employed in the adolescent arm of this cohort and highlight some of the initial accomplishments. We then outline in detail the phenotyping protocol used to acquire comparable data in the parents.

Improving recorded volume in mesial temporal lobe by optimizing stereotactic intracranial electrode implantation planning.

PURPOSE: Intracranial electrodes are sometimes implanted in patients with refractory epilepsy to identify epileptic foci and propagation. Maximal recording of EEG activity from regions suspected of seizure generation is paramount. However, the location of individual contacts cannot be considered with current manual planning approaches. We propose and validate a procedure for optimizing intracranial electrode implantation planning that maximizes the recording volume, while constraining trajectories to safe paths. METHODS: Retrospective data from 20 patients with epilepsy that had electrodes implanted in the mesial temporal lobes were studied. Clinical imaging data (CT/A and T1w MRI) were automatically segmented to obtain targets and structures to avoid. These data were used as input to the optimization procedure. Each electrode was modeled to assess risk, while individual contacts were modeled to estimate their recording capability. Ordered lists of trajectories per target were obtained. Global optimization generated the best set of electrodes. The procedure was integrated into a neuronavigation system. RESULTS: Trajectories planned automatically covered statistically significant larger target volumes than manual plans [Formula: see text]. Median volume coverage was [Formula: see text] for automatic plans versus [Formula: see text] for manual plans. Furthermore, automatic plans remained at statistically significant safer distance to vessels [Formula: see text] and sulci [Formula: see text]. Surgeon's scores of the optimized electrode sets indicated that 95% of the automatic trajectories would be likely considered for use in a clinical setting. CONCLUSIONS: This study suggests that automatic electrode planning for epilepsy provides safe trajectories and increases the amount of information obtained from the intracranial investigation.

Relating axonal injury to functional recovery in MS.

A patient was followed after the new onset of hemiparesis from relapse of MS with serial MR spectroscopy and functional MRI. The association of clinical improvement with recovery of N-acetylaspartate, a marker of neuronal integrity, and progressive reduction of abnormally large functional MRI cortical activation with movement demonstrates that dynamic reorganization of the motor cortex accompanies remission of MS.

Radiosurgery of cerebral arteriovenous malformations with the dynamic stereotactic irradiation.

From December 1986 through December 1988, 33 patients with inoperable arteriovenous malformation (AVM) were treated in our center with the dynamic stereotactic radiosurgery, which uses a standard 10 MV isocentric linear accelerator. There were 18 females and 15 males with a median age of 26 years (range: 9-69) and a median follow-up time of 16 months (range: 7-32). The arteriovenous malformation volumes treated ranged from 0.2 to 42 cm3. The prescribed doses at the isocenter varied from 50 to 55 Gy and were given as a single fraction in the majority of the patients (31/33). Late complications consisting of intracranial bleeding and/or hemiparesis were observed in three patients. To date, 21 patients underwent repeat angiographic studies at 1 year post-treatment. A complete obliteration of the lesion was achieved in 38% of these patients. For the patients whose arteriovenous malformation nidus was covered by a minimum dose of 25 Gy, the total obliteration rate was 61.5% (8/13), whereas none of the patients who had received less than 25 Gy at the edge of the nidus obtained a total obliteration. Our preliminary analysis at 1 year post-radiosurgery reveals results comparable to those previously reported for other radiosurgical techniques for the same follow-up period.

Radiosurgery with high energy photon beams: a comparison among techniques.

The presently known radiosurgical techniques with high energy photon beams are based either on the commercially available Gamma unit utilizing 201 stationary cobalt beams or on isocentric linear accelerators. The techniques using linear accelerators are divided into the single plane rotation, the multiple non-coplanar arcs, and the dynamic rotation. A brief description of these techniques is given, and their physical characteristics, such as precision of dose delivery, dose fall-off outside the target volume, and isodose distributions are discussed. It is shown that the multiple non-coplanar arcs technique and the dynamic rotation give dose distributions similar to those of the Gamma unit, which makes these two linear accelerator based techniques attractive alternatives to radiosurgery with the Gamma unit.

Radiosurgery with photon beams: physical aspects and adequacy of linear accelerators.

The question of the adequacy of isocentric linear accelerators (linacs) for use in radiosurgery is addressed. The general physical requirements for radiosurgery, mainly a high spatial and numerical accuracy of dose delivery, reasonable treatment time, and low skin and leakage dose as well as cost considerations are examined. Various linac-based procedures are analyzed in view of their ability to meet these requirements and are contrasted with the clinically proven system of the Gamma unit. It is shown that the linac-based multiple converging arcs techniques and the dynamic rotation meet the stringent physical requirements on dose delivery and are thus viable alternatives to radiosurgery with the commercially available and dedicated Gamma unit.

Oxidative metabolism and the detection of neuronal activation via imaging.

Recent years have witnessed a great growth of interest in non-invasive imaging methods, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), permitting identification of brain structures that mediate specific cognitive and behavioural tasks in humans. Because these techniques use physiological responses such as increased perfusion or metabolism as surrogate indicators of evoked neuronal electrical activity, understanding the role of these processes in sustaining the information processing function of neurons is vital to the proper interpretation of functional neuroimaging data. An ultimate goal of these non-invasive techniques is to approach the sensitivity and spatial resolution of earlier autoradiographic methods, which have repeatedly demonstrated exquisitely detailed delineations of neuronal response patterns using metabolic glucose uptake as a physiological tag. Although glucose is generally metabolized in conjunction with oxygen, technical challenges in imaging tissue oxygen consumption in vivo have limited the use of this complementary process in the detection of neuronal activation. In this article we review concepts linking cerebral blood flow and metabolism to neuronal activation, and compare functional imaging techniques that exploit these relationships. We also describe recently introduced MRI based methods for measurement of oxygen consumption and assess the relative contributions of different metabolic pathways during neuronal activation. Our calculations suggest that the bulk of the energy demand evoked during stimulation of neurons in visual cortex is met through oxidative metabolism of glucose, supporting the use of oxygen uptake as a marker for increased neuronal electrical activity.

Quantitative interpretation of magnetization transfer in spoiled gradient echo MRI sequences.

A method for analyzing general pulsed magnetization transfer (MT) experiments in which off-resonance saturation pulses are interleaved with on-resonance excitation pulses is presented. We apply this method to develop a steady-state signal equation for MT-weighted spoiled gradient echo sequences and consider approximations that facilitate its rapid computation. Using this equation, we assess various experimental designs for quantitatively imaging the fractional size of the restricted pool, cross-relaxation rate, and T(1) and T(2) relaxation times of the two pools in a binary spin bath system. From experiments on agar gel, this method is shown to reliably and accurately estimate the exchange and relaxation properties of a material in an imaging context, suggesting the feasibility of using this technique in vivo.

Magnetization transfer MR of the normal adult brain.

PURPOSE: To establish a normal baseline of the percent magnetization transfer of gray (cortical and deep) and white matter structures in the brain in healthy adults and to determine whether there are adult age-related differences in these measurements. METHODS: Axial T1-weighted scans (800/20 [repetition time/echo time]) with and without magnetization transfer were prospectively performed on a 1.5-T MR imaging unit on 68 healthy patients (aged 20 to 76 years). Presaturation and postsaturation magnetization transfer images were obtained using an on-resonance binomial pulse. All patients had normal MR scans on all pulse sequences. A calculated "difference" image was used to calculate the percent magnetization transfer in multiple specific regions of the brain. In each hemisphere, 9 discrete areas of cortical and deep gray matter and 29 areas of white matter were measured in 68 patients to generate age-related changes in percent magnetization transfer in these anatomic regions. Ranges of normal percent magnetization transfer in each of the 38 measures were established. RESULTS: The percent magnetization transfer of the gray matter (28% +/- 2%) was lower than that of the white matter (36% +/- 2%). There was no statistically significant difference in the percent magnetization transfer in different areas of gray matter. Deep white matter in the different lobes (percent magnetization transfer, 31% to 38%) also showed no differences by age. Percent magnetization transfer was the highest in the genu of the corpus callosum (42%), and this was statistically significant compared with other white matter measurements. CONCLUSION: There were no statistically significant age-related variations in the percent magnetization transfer in healthy adults in gray or white matter. These percent magnetization transfer measurements provide baseline normative data, which can be used to measure the extent and severity of white matter changes in disease states.

Improved detection of enhancing and nonenhancing lesions of multiple sclerosis with magnetization transfer.

PURPOSE: To determine whether magnetization transfer imaging can improve visibility of contrast enhancement of multiple sclerosis plaques. METHODS: Fifty-nine enhancing and 63 nonenhancing lesions in 10 patients with multiple sclerosis were evaluated to calculate contrast-to-noise ratios on conventional T1-weighted and T1-weighted magnetization transfer images. The signal intensity of the lesion and the background (white matter) were measured on precontrast T1-weighted and T1-weighted magnetization transfer images (800/20/1 [repetition time/echo time/excitations]) and on postcontrast T1-weighted and T1-weighted magnetization transfer images. Mean contrast-to-noise ratios was calculated for all lesions. RESULTS: The contrast-to-noise ratio was significantly higher for enhancing and nonenhancing lesions on T1-weighted magnetization transfer images than on conventional T1-weighted images. For enhancing lesions, the contrast-to-noise ratio was significantly higher on postcontrast T1-weighted magnetization transfer images, 32 +/- 2 compared with 21 +/- 2 on conventional T1-weighted images. Fifty of the 59 enhancing lesions were seen on both the T1-weighted and the T1-weighted magnetization transfer images. Nine enhancing lesions were seen only on the postcontrast T1-weighted magnetization transfer images. In addition, of 63 nonenhancing lesions seen on proton-density, T2-weighted, and T1-weighted magnetization transfer images, 16 were not seen on the conventional T1-weighted images. Seven of the 63 nonenhancing lesions and 7 of the 59 enhancing lesions had high signal intensity on the precontrast T1-weighted magnetization transfer images suggestive of lipid signal, a finding not seen on the conventional precontrast T1-weighted images. CONCLUSION: Magnetization transfer improves the visibility of enhancing multiple sclerosis lesions, because they have a higher contrast-to-noise ratio than conventional postcontrast T1-weighted images. High signal intensity on both nonenhancing and enhancing lesions noted only on precontrast T1-weighted magnetization transfer suggests a lipid signal was unmasked. If magnetization transfer is used in multiple sclerosis patients, a precontrast magnetization transfer image is necessary.

Measure of magnetization transfer in multiple sclerosis demyelinating plaques, white matter ischemic lesions, and edema.

PURPOSE: To define the percentage of magnetization transfer of multiple sclerosis (MS) plaques, ischemic white matter lesions, and vasogenic edema to determine whether this measurement can help differentiate these entities. METHODS: Findings were compared in 25 patients with proved MS, 20 patients with white matter ischemic lesions, and 72 patients with white matter edema (caused by tumors, infections, or acute/subacute infarctions) in the periventricular system, centrum semiovale, and subcortical white matter. Magnetization transfer was performed using an on-resonance binomial pulse. The percentage of magnetization transfer of the normal white matter was also calculated. RESULTS: Magnetization transfer was significantly higher in white matter ischemic lesions (range, 31% to 38%; mean, 34% +/- 0.6%) than in demyelinating plaques of MS (range, 19% to 28%; mean, 22.5% +/- 1%) and in edema (range, 29% to 37%; mean, 30.2% +/- 0.4%). No statistical difference in percentage of magnetization transfer was found among lesions in the periventricular system (34% +/- 0.6%), centrum semiovale (35% +/- 0.5%), or subcortical white matter (33% +/- 0.6%), or in vasogenic edema associated with tumors, infections, or infarction. CONCLUSION: Differences in magnetization transfer suggest less change of demyelination in white matter ischemic lesions than in MS plaques and are significantly different in this respect from similar MS plaques. Magnetization transfer of edema was less than that of normal white matter or fell between ischemic abnormalities and MS plaques. Percentages of magnetization transfer below the mid-20% range is highly suggestive of demyelination. Vasogenic edema, our surrogate for increased water content of white matter, caused a decrease in the percentage of magnetization transfer.