Relationship between M100 Auditory Evoked Response and Auditory Radiation Microstructure in 16p11.2 Deletion and Duplication Carriers.

BACKGROUND AND PURPOSE: Deletion and duplication of chromosome 16p11.2 (BP4-BP5) have been associated with developmental disorders such as autism spectrum disorders, and deletion subjects exhibit a large (20-ms) delay of the auditory evoked cortical response as measured by magnetoencephalography (M100 latency). The purpose of this study was to use a multimodal approach to test whether changes in white matter microstructure are associated with delayed M100 latency. MATERIALS AND METHODS: Thirty pediatric deletion carriers, 9 duplication carriers, and 39 control children were studied with both magnetoencephalography and diffusion MR imaging. The M100 latency and auditory system DTI measures were compared between groups and tested for correlation. RESULTS: In controls, white matter diffusivity significantly correlated with the speed of the M100 response. However, the relationship between structure and function appeared uncoupled in 16p11.2 copy number variation carriers. The alterations to auditory system white matter microstructure in the 16p11.2 deletion only partially accounted for the 20-ms M100 delay. Although both duplication and deletion groups exhibit abnormal white matter microstructure, only the deletion group has delayed M100 latency. CONCLUSIONS: These results indicate that gene dosage impacts factors other than white matter microstructure, which modulate conduction velocity.

Left hemisphere diffusivity of the arcuate fasciculus: influences of autism spectrum disorder and language impairment.

BACKGROUND AND PURPOSE: There has been much discussion whether brain abnormalities associated with specific language impairment and autism with language impairment are shared or are disorder specific. Although white matter tract abnormalities are observed in both specific language impairment and autism spectrum disorders, the similarities and differences in the white matter abnormalities in these 2 disorders have not been fully determined. MATERIALS AND METHODS: Diffusion tensor imaging diffusion parameters of the arcuate fasciculus were measured in 14 children with specific language impairment as well as in 16 children with autism spectrum disorder with language impairment, 18 with autism spectrum disorder without language impairment, and 25 age-matched typically developing control participants. RESULTS: Language impairment and autism spectrum disorder both had (elevating) main effects on mean diffusivity of the left arcuate fasciculus, initially suggesting a shared white matter substrate abnormality. Analysis of axial and radial diffusivity components, however, indicated that autism spectrum disorder and language impairment differentially affect white matter microstructural properties, with a main effect of autism spectrum disorder on axial diffusivity and a main effect of language impairment on radial diffusivity. CONCLUSIONS: Although white matter abnormalities appear similar in language impairment and autism spectrum disorder when examining broad white matter measures, a more detailed analysis indicates different mechanisms for the white matter microstructural anomalies associated with language impairment and autism spectrum disorder.

High angular resolution diffusion imaging probabilistic tractography of the auditory radiation.

BACKGROUND AND PURPOSE: The auditory radiation crosses other white matter tracts and cannot reliably be delineated or quantitatively assessed with DTI fiber tracking. This study investigates whether HARDI fiber tracking can be used to robustly delineate the full extent of the tract. MATERIALS AND METHODS: HARDI (64-direction, b=3000 s/mm²) and DTI (30-direction, b=1000 s/mm²) were acquired from 25 control participants between 8 and 26 years old. Probabilistic HARDI and DTI fiber tracking of the auditory radiation was performed with starting and filter regions automatically generated from the FreeSurfer white matter parcellation. DTI fiber tracking was performed with both the 64-direction and the 30-direction datasets. Fiber-tracking trials demonstrating connectivity from the Heschl gyrus to the medial geniculate nucleus were considered successful. RESULTS: The HARDI fiber tracking success rate was 98% and was significantly higher than the 64-direction DTI rate of 50% or the 30-direction DTI rate of 42% (P < .001). The success rates of HARDI fiber tracking for the left and right auditory radiations were not significantly different. In contrast, the left auditory radiation was successfully delineated with DTI fiber tracking at a higher rate than the right auditory radiation. CONCLUSIONS: HARDI can discriminate the complex white matter pathways at the junction of the auditory radiation and the ILF. HARDI fiber tracking can reliably delineate the auditory radiation.

Diffusion-weighted imaging in fetuses with severe congenital heart defects.

Fetal diffusion MR imaging was performed in 3 fetuses with CHD. ADC values in the periatrial WM, thalamus, and basal ganglia were compared with those in a control population of fetuses. Diffusivity in the periatrial WM and thalamus was higher for the fetuses with CHD compared with controls. These observations support the finding of abnormal in utero brain development in fetuses with CHD.

Quantitative fiber tracking of the optic radiation is correlated with visual-evoked potential amplitude in preterm infants.

BACKGROUND AND PURPOSE: Children born preterm are at risk for adverse outcome, including visual impairment. We examined the relationship between neonatal DTI and sVEP in children born preterm to determine whether visual outcomes are related to early measurements of brain microstructure. MATERIALS AND METHODS: Subjects were born at <34 weeks gestation and imaged before term-equivalent age. DTI fiber tracking was used to delineate the optic radiations and measure tract-specific average FA, D(av), and parallel and transverse diffusivity. Visual-evoked response amplitudes were measured as a function of spatial frequency, contrast, and vernier offset size with sVEP at 6-20 months after birth. The association between DTI and sVEP was assessed by using the Spearman correlation coefficient and linear regression for repeated measures. RESULTS: Nine children with 15 scans were included. The peak response amplitudes for spatial frequency sweeps were associated with increasing FA and decreasing D(av) and transverse diffusivity (P ≤ .006) but not with parallel diffusivity (P = 1). There was only modest association with the swept contrast condition and no detectable association with the vernier offset sweeps. CONCLUSIONS: Microstructure of the optic radiations measured shortly after birth is associated with quantitatively measured responses elicited by moderate-to-high contrast spatiotemporal gratings in infancy. These findings are in keeping with studies showing a relationship between brain microstructure and function. While the clinical impact is not known, quantitative neuroimaging of white matter may ultimately be important for predicting outcome in preterm neonates.

Diffusion-weighted imaging in fetuses with unilateral cortical malformations and callosal agenesis.

DWI was performed in fetuses with callosal agenesis and unilateral cortical malformations. ADC values were retrospectively measured in the developing white matter underlying the cortical malformation and compared with the corresponding contralateral white matter. In all 3 patients, ADC values were lower under the areas of cortical malformation compared with the normal contralateral side. Our findings suggest that there are structural differences in the developing white matter underlying areas of cortical malformation.

Normative apparent diffusion coefficient values in the developing fetal brain.

BACKGROUND AND PURPOSE: Previous studies of diffusion-weighted imaging (DWI) in fetuses are limited. Because of the need for normative data for comparison with young fetuses and preterm neonates with suspected brain abnormalities, we studied apparent diffusion coefficient (ADC) values in a population of singleton, nonsedated, healthy fetuses. MATERIALS AND METHODS: DWI was performed in 28 singleton nonsedated fetuses with normal or questionably abnormal results on sonography and normal fetal MR imaging results; 10 fetuses also had a second fetal MR imaging, which included DWI. ADC values in the periatrial white matter (WM), frontal WM, thalamus, basal ganglia, cerebellum, and pons were plotted against gestational age and analyzed with linear regression. We compared mean ADC in different regions using the Tukey Honestly Significant Difference test. We also compared rates of decline in ADC with increasing gestational age across different areas by using the t test with multiple comparisons correction. Neurodevelopmental outcome was assessed. RESULTS: Median gestational age was 24.28 weeks (range, 21-33.43 weeks). Results of all fetal MR imaging examinations were normal, including 1 fetus with a normal variant of a cavum velum interpositum. ADC values were highest in the frontal and periatrial WM and lowest in the thalamus and pons. ADC declined with increasing gestational age in periatrial WM (P = .0003), thalamus (P < .0001), basal ganglia (P = .0035), cerebellum (P < .0001), and pons (P = .024). Frontal WM ADC did not significantly change with gestational age. ADC declined fastest in the cerebellum, followed by the thalamus. CONCLUSIONS: Regional differences in nonsedated fetal ADC values and their evolution with gestational age likely reflect differences in brain maturation and are similar to published data in premature neonates.

Quantitative fiber tracking analysis of the optic radiation correlated with visual performance in premature newborns.

BACKGROUND AND PURPOSE: Many prematurely born neonates have abnormalities of vision or visual processing. This study tests the hypothesis that a correlation exists between the microstructure of the optic radiation and visual performance in premature neonates. MATERIALS AND METHODS: Diffusion tensor imaging (DTI) was performed on 36 premature neonates ranging in age from 29 to 41 weeks of gestational age (GA) at time of MR imaging. DTI fiber tracking methods were developed to delineate the optic radiations and segment the tract into anterior, middle, and posterior regions. Structural development and spatial heterogeneity in the delineated optic radiations were quantitatively assessed with diffusion tensor parameters including fractional anisotropy (FA), directionally averaged diffusivity (D(av)), parallel diffusivity (lambda(1)), and transverse diffusivity (lambda( perpendicular)). Visual maturity of the preterm neonates at the time of MR imaging was assessed with a visual fixation task. Regression analysis was used to examine the relationship between neonatal visual performance and the microstructure of the optic radiation. RESULTS: Fractional anisotropy within the optic radiation was observed to increase with GA (P < .0001). D(av), parallel diffusivity, and transverse diffusivity within the optic radiation each decreased with GA (P < .0003, P < .02, and P < .0001, respectively). The anterior segment of the optic radiation exhibited higher FA and lower D(av), parallel diffusivity, and transverse diffusivity (P < .005 each) than within the middle and posterior segments. Optic radiation fractional anisotropy correlated significantly with scores from the visual fixation tracking assessment, independent of GA (P < .006). CONCLUSIONS: This study detected a significant link between the tissue architecture of the optic radiation and visual function in premature neonates.

Diffusion tensor imaging of the pyramidal tracts in infants with motor dysfunction.

OBJECTIVE: To determine if diffusion tensor imaging (DTI) metrics of the pyramidal tracts correlate with motor outcome in infants presenting with motor dysfunction. METHODS: DTI tractography of the pyramidal tracts was performed in 21 patients with clinical motor dysfunction who were less than 30 months of age and in 22 age-matched controls. We plotted tract-specific DTI metrics (fractional anisotropy, parallel diffusivity, transverse diffusivity, and mean diffusivity) against age for the controls and generated normative curves. For each patient, we calculated the deviation from the normative curves. Patients returned for a neurodevelopmental evaluation when they were over 36 months of age, and motor outcome measures were performed. We analyzed the association between normative deviation in DTI metrics and motor outcome measures using linear and logistic regression models. RESULTS: Normative deviation in fractional anisotropy and transverse diffusivity were significantly correlated with all measures of motor outcome. Lower fractional anisotropy and higher transverse diffusivity compared to controls were associated with worse motor outcome. Furthermore, children who were eventually diagnosed with permanent motor dysfunction had lower fractional anisotropy and higher transverse diffusivity compared with those whose motor dysfunction normalized. CONCLUSIONS: Diffusion tensor imaging metrics correlate with motor outcome in infants presenting with motor dysfunction. The identification of a quantitative imaging marker that can be applied to infants at the time of clinical presentation has implications for the evaluation of early motor dysfunction.

Diffusion tensor MR imaging and fiber tractography: technical considerations.

This second article of the 2-part review builds on the theoretic background provided by the first article to cover the major technical factors that affect image quality in diffusion imaging, including the acquisition sequence, magnet field strength, gradient amplitude, and slew rate as well as multichannel radio-frequency coils and parallel imaging. The sources of many common diffusion image artifacts are also explored in detail. The emphasis is on optimizing these technical factors for state-of-the-art diffusion-weighted imaging and diffusion tensor imaging (DTI) based on the best available evidence in the literature. An overview of current methods for quantitative analysis of DTI data and fiber tractography in clinical research is also provided.

Diffusion tensor MR imaging and fiber tractography: theoretic underpinnings.

In this article, the underlying theory of clinical diffusion MR imaging, including diffusion tensor imaging (DTI) and fiber tractography, is reviewed. First, a brief explanation of the basic physics of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) mapping is provided. This is followed by an overview of the additional information that can be derived from the diffusion tensor, including diffusion anisotropy, color-encoded fiber orientation maps, and 3D fiber tractography. This article provides the requisite background for the second article in this 2-part review to appear next month, which covers the major technical factors that affect image quality in diffusion MR imaging, including the acquisition sequence, magnet field strength, gradient amplitude and slew rate, and multichannel radio-frequency coils and parallel imaging. The emphasis is on optimizing these factors for state-of-the-art DWI and DTI based on the best available evidence in the literature.

Diffusion tensor MR imaging tractography of the pyramidal tracts correlates with clinical motor function in children with congenital hemiparesis.

BACKGROUND AND PURPOSE: Children with congenital hemiparesis have greater asymmetry in diffusion parameters of the pyramidal tracts compared with control subjects. We hypothesized that the asymmetry correlates with the severity of hemiparesis and that diffusion metrics would be abnormal in the affected tracts and normal in the unaffected tracts. MATERIALS AND METHODS: Fifteen patients with congenital hemiparesis and 17 age-matched control subjects were studied with diffusion tensor MR imaging tractography. Hemipareses were scored as mild, moderate, or severe. We measured tract-specific diffusion parameters (fractional anisotropy, mean, and directional diffusion coefficients) of the pyramidal tracts. We compared tract-specific parameters and asymmetry between the right and left tracts of the differing severity groups and control subjects. RESULTS: We observed many different causes of congenital hemiparesis including venous infarction, arterial infarction, and polymicrogyria. Clinical severity of hemiparesis correlated with asymmetry in fractional anisotropy (P < .0001), transverse diffusivity (P < .0001), and mean diffusivity (P < .03). With increasing severity of hemiparesis, fractional anisotropy decreased (P < .0001) and transverse diffusivity (P < .0001) and mean diffusivity (P < .02) increased in the affected pyramidal tract compared with controls. Diffusion metrics in the unaffected tract were similar to those in the control subjects. CONCLUSION: Asymmetry in fractional anisotropy, transverse diffusivity, and mean diffusivity, as well as the degree of abnormality in the actual values of the affected pyramidal tracts themselves, correlates with the severity of motor dysfunction in infants and children with congenital hemiparesis from different causes. This suggests that abnormalities detected by diffusion tensor MR imaging tractography in the affected pyramidal tract are related to the functional ability of the affected pyramidal tract, regardless of the etiology of motor dysfunction.

Characterization of experimental spinal cord injury with magnetization transfer ratio histograms.

This study was designed to characterize the severity of tissue damage in experimental spinal cord injury using magnetization transfer (MT) histogram analysis. Seven Sprague-Dawley rats were subjected to laminectomy and standard weight-drop injury to the spinal cord (four rats at 15 cm drop-height and three rats at 2.5 cm). Three control animals underwent laminectomy without weight-drop. After sacrifice, the animals were scanned at 1.9 T with a pulsed off-resonance MT technique. Following magnetic resonance (MR) imaging, the cords were embedded in paraffin and sectioned into 5-microm sections for semiquantitative histopathological analysis. Composite histograms were generated using data spanning an axial distance of 3 cm centered on the injury site. MT histogram parameters, such as the amount of tissue with statistical correspondence to normal white matter, were highly predictive of histopathological results, including myelination state and neurofilament damage. Less correlation with edema was observed, suggesting that the technique was most sensitive to true tissue alteration.

Anthem Blue Cross and Blue Shield's coronary services network: a managed care organization's approach to improving the quality of cardiac care for its members.

OBJECTIVE: To describe a managed care organization's efforts to improve value for its members by forming a coronary services network (CSN). DESIGN: To identify high-quality facilities for its CSN, Anthem Blue Cross and Blue Shield reviewed claims data and clinical data from hospitals that met its general quality standards. An external firm measured and risk-adjusted applicant hospitals' mortality rates. Hospitals that demonstrated superior performance were eligible to join the CSN. In 1996, 2 years after the CSN was formed, clinical outcomes of participants and new applicants were analyzed again by the same external firm. PATIENTS AND METHODS: Data on more than 10,000 consecutive (all-payer) inpatients discharged after coronary bypass surgery in 1993 were collected from 16 applicant hospitals using a uniform format and data definitions. This analysis was expanded to 23 participating and applicant hospitals that discharged more than 13,000 patients who underwent either bypass surgery or coronary revascularization in 1995. We compared risk-adjusted routine length of stay (a measure of efficiency), mortality rates, and adverse outcome rates between CSN and non-CSN facilities. RESULTS: From 1993 to 1995, overall length of stay in the network decreased by 20%, from 12.3 to 9.8 days (P < or = 0.01) and severity-adjusted mortality rates decreased by 7.3%, from 2.9% to 2.7%. Initially, facilities outside the network had comparable efficiency but much higher mortality. However, they improved so much in both measures that their severity-adjusted mortality rate for bypass surgery in 1995 was no more than 10% higher than that of CSN hospitals. CONCLUSION: The creation of a statewide CSN that emphasized and improved the level of performance among providers ultimately benefited the carrier's managed care members. The desirability of participation was evidenced by an increase in the number of applicant hospitals over the 2 years. This may have stimulated quality improvement among competing providers in the region and among CSN facilities themselves.

Forming a coronary services network on the basis of quality of care.

An Ohio insurance company's initiative to emphasize risk-adjusted clinical outcomes as criteria for selecting and reimbursing members of a network is stimulating a new emphasis on quality of care throughout the market area. Hospitals inside the network are cooperating to improve their collective results, while providers on the outside have launched major quality improvement programs in the effort to become measurably competitive with these centers of excellence. This case study in network selection demonstrates a new role for fiscal intermediaries in health care.

Bulk laxative ileus.

In an elderly nursing home resident who had taken excessive dosages of bulk laxative for many years, small-bowel obstruction developed, requiring surgical intervention. A carcinoma of the ascending colon probably was the immediate cause of the obstruction, which resulted in the accumulation and inspissation of the bulk laxative throughout the small bowel. Great care should be exercised in the long-term use of these laxatives.