Identification of the Language Network from Resting-State fMRI in Patients with Brain Tumors: How Accurate Are Experts?

BACKGROUND AND PURPOSE: Resting-state fMRI helps identify neural networks in presurgical patients who may be limited in their ability to undergo task-fMRI. The purpose of this study was to determine the accuracy of identifying the language network from resting-state-fMRI independent component analysis (ICA) maps. MATERIALS AND METHODS: Through retrospective analysis, patients who underwent both resting-state-fMRI and task-fMRI were compared by identifying the language network from the resting-state-fMRI data by 3 reviewers. Blinded to task-fMRI maps, these investigators independently reviewed resting-state-fMRI ICA maps to potentially identify the language network. Reviewers ranked up to 3 top choices for the candidate resting-state-fMRI language map. We evaluated associations between the probability of correct identification of the language network and some potential factors. RESULTS: Patients included 29 men and 14 women with a mean age of 41 years. Reviewer 1 (with 17 years' experience) demonstrated the highest overall accuracy with 72%; reviewers 2 and 3 (with 2 and 7 years' experience, respectively) had a similar percentage of correct responses (50% and 55%). The highest accuracy used ICA50 and the top 3 choices (81%, 65%, and 60% for reviewers 1, 2, and 3, respectively). The lowest accuracy used ICA50, limiting each reviewer to the top choice (58%, 35%, and 42%). CONCLUSIONS: We demonstrate variability in the accuracy of blinded identification of resting-state-fMRI language networks across reviewers with different years of experience.

Bias in Neuroradiology Peer Review: Impact of a "Ding" on "Dinging" Others.

BACKGROUND AND PURPOSE: The validity of radiology peer review requires an unbiased assessment of studies in an environment that values the process. We assessed radiologists' behavior reviewing colleagues' reports. We hypothesized that when a radiologist receives a discrepant peer review, he is more likely to submit a discrepant review about another radiologist. MATERIALS AND METHODS: We analyzed the anonymous peer review submissions of 13 neuroradiologists in semimonthly blocks of time from 2016 to 2018. We defined a discrepant review as any one of the following: 1) detection miss, clinically significant; 2) detection miss, clinically not significant; 3) interpretation miss, clinically significant; or 4) interpretation miss, clinically not significant. We used random-effects Poisson regression analysis to determine whether a neuroradiologist was more likely to submit a discrepant report during the semimonthly block in which he or she received one versus the semimonthly block thereafter. RESULTS: Four hundred sixty-eight discrepant peer review reports were submitted; 161 were submitted in the same semimonthly block of receipt of a discrepant report and 325 were not. Receiving a discrepant report had a positive effect on submitting discrepant reports: an expected relative increase of 14% (95% CI, 8%-21%). Notably, receiving a clinically not significant discrepant report (coefficient = 0.13; 95% CI, 0.05-0.22) significantly and positively correlated with submitting a discrepant report within the same time block, but this was not true of clinically significant reports. CONCLUSIONS: The receipt of a clinically not significant discrepant report leads to a greater likelihood of submitting a discrepant report. The motivation for such an increase should be explored for potential bias.

Presurgical Brain Mapping of the Ventral Somatomotor Network in Patients with Brain Tumors Using Resting-State fMRI.

BACKGROUND AND PURPOSE: Resting-state fMRI readily identifies the dorsal but less consistently the ventral somatomotor network. Our aim was to assess the relative utility of resting-state fMRI in the identification of the ventral somatomotor network via comparison with task-based fMRI in patients with brain tumor. MATERIALS AND METHODS: We identified 26 surgically naïve patients referred for presurgical fMRI brain mapping who had undergone both satisfactory ventral motor activation tasks and resting-state fMRI. Following standard preprocessing for task-based fMRI and resting-state fMRI, general linear model analysis of the ventral motor tasks and independent component analysis of resting-state fMRI were performed with the number of components set to 20, 30, 40, and 50. Visual overlap of task-based fMRI and resting-state fMRI at different component levels was assessed and categorized as full match, partial match, or no match. Rest-versus-task-fMRI concordance was calculated with Dice coefficients across varying fMRI thresholds before and after noise removal. Multithresholded Dice coefficient volume under the surface was calculated. RESULTS: The ventral somatomotor network was identified in 81% of patients. At the subject level, better matches between resting-state fMRI and task-based fMRI were seen with an increasing order of components (53% of cases for 20 components versus 73% for 50 components). Noise-removed group-mean volume under the surface improved as component numbers increased from 20 to 50, though ANOVA demonstrated no statistically significant difference among the 4 groups. CONCLUSIONS: In most patients, the ventral somatomotor network can be identified with an increase in the probability of a better match at a higher component number. There is variable concordance of the ventral somatomotor network at the single-subject level between resting-state and task-based fMRI.

Lesion Heterogeneity on High-Field Susceptibility MRI Is Associated with Multiple Sclerosis Severity.

BACKGROUND AND PURPOSE: Susceptibility MR imaging contrast variations reflect alterations in brain iron and myelin content, making this imaging tool relevant to studies of multiple sclerosis lesion heterogeneity. In this study, we aimed to characterize the relationship of high-field, susceptibility contrasts in multiple sclerosis lesions to clinical outcomes. MATERIALS AND METHODS: Twenty-four subjects with multiple sclerosis underwent 7T MR imaging of the brain, disability examinations, and a fatigue inventory. The inverse of T2* relaxation time (R2*), frequency, and relative susceptibility (from quantitative susceptibility mapping) were analyzed in 306 white matter lesions. RESULTS: Most lesions were hypointense on R2* (88% without a rim, 5% with). Lesions that were hyperintense on quantitative susceptibility mapping were more frequent in relapsing-remitting than in progressive multiple sclerosis (54% versus 35%, P = .018). Hyperintense lesion rims on quantitative susceptibility maps were more common in progressive multiple sclerosis and patients with higher levels of disability and fatigue. Mean lesion R2* was inversely related to disability and fatigue and significantly reduced in progressive multiple sclerosis. Relative susceptibility was lower in lesions in progressive multiple sclerosis (median, -0.018 ppm; range, -0.070 to 0.022) than in relapsing-remitting MS (median, -0.010 ppm; range, -0.062 to 0.052; P = .003). CONCLUSIONS: A progressive clinical phenotype and greater disability and fatigue were associated with lower R2* and relative susceptibility values (suggestive of low iron due to oligodendrocyte loss) and rimmed lesions (suggestive of chronic inflammation) in this multiple sclerosis cohort. Lesion heterogeneity on susceptibility MR imaging may help explain disability in multiple sclerosis and provide a window into the processes of demyelination, oligodendrocyte loss, and chronic lesion inflammation.

Quantifying the reliability of image replication studies: the image intraclass correlation coefficient (I2C2).

This article proposes the image intraclass correlation (I2C2) coefficient as a global measure of reliability for imaging studies. The I2C2 generalizes the classic intraclass correlation (ICC) coefficient to the case when the data of interest are images, thereby providing a measure that is both intuitive and convenient. Drawing a connection with classical measurement error models for replication experiments, the I2C2 can be computed quickly, even in high-dimensional imaging studies. A nonparametric bootstrap procedure is introduced to quantify the variability of the I2C2 estimator. Furthermore, a Monte Carlo permutation is utilized to test reproducibility versus a zero I2C2, representing complete lack of reproducibility. Methodologies are applied to three replication studies arising from different brain imaging modalities and settings: regional analysis of volumes in normalized space imaging for characterizing brain morphology, seed-voxel brain activation maps based on resting-state functional magnetic resonance imaging (fMRI), and fractional anisotropy in an area surrounding the corpus callosum via diffusion tensor imaging. Notably, resting-state fMRI brain activation maps are found to have low reliability, ranging from .2 to .4. Software and data are available to provide easy access to the proposed methods.

MELD Exceptions and Rates of Waiting List Outcomes.

Model for End-stage Liver Disease (MELD)-based allocation of deceased donor livers allows exceptions for patients whose score may not reflect their true mortality risk. We hypothesized that organ procurement organizations (OPOs) may differ in exception practices, use of exceptions may be increasing over time, and exception patients may be advantaged relative to other patients. We analyzed longitudinal MELD score, exception and outcome in 88 981 adult liver candidates as reported to the United Network for Organ Sharing from 2002 to 2010. Proportion of patients receiving an HCC exception was 0-21.4% at the OPO-level and 11.9-18.8% at the region level; proportion receiving an exception for other conditions was 0.0%-13.1% (OPO-level) and 3.7-9.5 (region-level). Hepatocellular carcinoma (HCC) exceptions rose over time (10.5% in 2002 vs. 15.5% in 2008, HR = 1.09 per year, p<0.001) as did other exceptions (7.0% in 2002 vs. 13.5% in 2008, HR = 1.11, p<0.001). In the most recent era of HCC point assignment (since April 2005), both HCC and other exceptions were associated with decreased risk of waitlist mortality compared to nonexception patients with equivalent listing priority (multinomial logistic regression odds ratio [OR] = 0.47 for HCC, OR = 0.43 for other, p<0.001) and increased odds of transplant (OR = 1.65 for HCC, OR = 1.33 for other, p<0.001). Policy advantages patients with MELD exceptions; differing rates of exceptions by OPO may create, or reflect, geographic inequity.

Longitudinal changes in diffusion tensor-based quantitative MRI in multiple sclerosis.

OBJECTIVE: To estimate longitudinal changes in a quantitative whole-brain and tract-specific MRI study of multiple sclerosis (MS), with the intent of assessing the feasibility of this approach in clinical trials. METHODS: A total of 78 individuals with MS underwent a median of 3 scans over 2 years. Diffusion tensor imaging indices, magnetization transfer ratio, and T2 relaxation time were analyzed in supratentorial brain, corpus callosum, optic radiations, and corticospinal tracts by atlas-based tractography. Linear mixed-effect models estimated annualized rates of change for each index, and sample size estimates for potential clinical trials were determined. RESULTS: There were significant changes over time in fractional anisotropy and perpendicular diffusivity in the supratentorial brain and corpus callosum, mean diffusivity in the supratentorial brain, and magnetization transfer ratio in all areas studied. Changes were most rapid in the corpus callosum, where fractional anisotropy decreased 1.7% per year, perpendicular diffusivity increased 1.2% per year, and magnetization transfer ratio decreased 0.9% per year. The T2 relaxation time changed more rapidly than diffusion tensor imaging indices and magnetization transfer ratio but had higher within-participant variability. Magnetization transfer ratio in the corpus callosum and supratentorial brain declined at an accelerated rate in progressive MS relative to relapsing-remitting MS. Power analysis yielded reasonable sample sizes (on the order of 40 participants per arm or fewer) for 1- or 2-year trials. CONCLUSIONS: Longitudinal changes in whole-brain and tract-specific diffusion tensor imaging indices and magnetization transfer ratio can be reliably quantified, suggesting that small clinical trials using these outcome measures are feasible.

MRI of the corpus callosum in multiple sclerosis: association with disability.

Inflammatory demyelination and axon damage in the corpus callosum are prominent features of multiple sclerosis (MS) and may partially account for impaired performance on complex tasks. The objective of this article was to characterize quantitative callosal MRI abnormalities and their association with disability. In 69 participants with MS and 29 healthy volunteers, lesional and extralesional callosal MRI indices were estimated via diffusion tensor tractography. expanded disability status scale (EDSS) and MS functional composite (MSFC) scores were recorded in 53 of the participants with MS. All tested callosal MRI indices were diffusely abnormal in MS. EDSS score was correlated only with age (r = 0.51). Scores on the overall MSFC and its paced serial auditory addition test (PASAT) and 9-hole peg test components were correlated with callosal fractional anisotropy (r = 0.27, 0.35, and 0.31, respectively) and perpendicular diffusivity (r = -0.29, -0.30, and -0.31) but not with overall callosal volume or callosal lesion volume; the PASAT score was more weakly correlated with callosal magnetization-transfer ratio (r = 0.21). Anterior callosal abnormalities were associated with impaired PASAT performance and posterior abnormalities with slow performance on the 9-hole peg test. In conclusion, abnormalities in the corpus callosum can be assessed with quantitative MRI and are associated with cognitive and complex upper-extremity dysfunction in MS.

Intelligence and medial temporal lobe function in older adults: a functional MR imaging-based investigation.

BACKGROUND AND PURPOSE: The influence of general intelligence and formal education on functional MR imaging (fMRI) activation has not been thoroughly studied in older adults. Although these factors could be controlled for through study design, this approach makes sample selection more difficult and reduces power. This study was undertaken to examine our hypothesis that intelligence and education would impact medial temporal lobe (MTL) fMRI responses to an episodic memory task in healthy elderly subjects. MATERIALS AND METHODS: Thirty-six women and 38 men, 50-83 years of age (mean, 63.4 +/- 7.9 years), completed an auditory paired-associates paradigm in a 1.5T magnet. The amplitude and volume of fMRI activation for both the right and left MTLs and MTL subregions were correlated with the intelligence quotients (IQs) and educational levels by using Pearson correlation coefficient tests and regression analyses. RESULTS: The participants' mean estimated full scale IQ and verbal IQ scores were 110.4 +/- 7.6 (range, 92-123) and 108.9 +/- 8.7 (range, 88-123), respectively. The years of education showed a mean of 16.1 +/- 3.2 years (range, 8-25 years). The paradigm produced significant activation in the MTL and subregions. However, the volume and amplitude of activation were unrelated to either IQ or years of schooling in men and/or women. CONCLUSIONS: We found no evidence of an effect of IQ or education on either the volume or amplitude of fMRI activation, suggesting that these factors do not necessarily need to be incorporated into study design or considered when evaluating other group relationships with fMRI.

Effect of semen sampling frequency on seminal antiretroviral drug concentration.

Study of male genital tract (MGT) pharmacology is relevant to the treatment of prostatitis, prostate cancer, infertility, and seminal human immunodeficiency virus transmission. However, the time course of drug concentrations in the MGT is largely unknown. To determine the feasibility of frequent semen sampling in assessing the pharmacokinetics of the MGT, we administered efavirenz, indinavir, and zidovudine to subjects to achieve steady-state levels and then collected semen samples at sequentially decreasing ejaculation intervals. The volume of seminal plasma decreased from 4.0 (1.2-5.1) ml (median with range) at 48 h after the baseline ejaculation to 0.72 (0.45-1.6) ml 1 h after a previous ejaculation, which was still adequate for drug concentration assessment. The seminal fructose concentration also decreased. However, the concentration of prostate-specific antigen and all three drugs did not decrease, even if the ejaculation intervals decreased to 1 h. Thus, semi-intensive semen sampling can be used to assess MGT pharmacokinetics.

Monte carlo conditional inference for log-linear and logistic models: a survey of current methodology.

Nuisance parameters are parameters that are not of immediate interest to the experimenter. For log-linear and logistic models the null distribution of (most) statistics of interest depends on such parameters. Traditionally, nuisance parameters were eliminated by performing inference with respect to the chi-squared limiting distribution of common test statistics. An alternative solution is to eliminate the nuisance parameters by conditioning on their minimal sufficient statistics. The support of the resulting conditional distribution is often intractable, making null probability calculations challenging. An often feasible way to avoid complete enumeration of this support is to approximate conditional probabilities using Monte Carlo methods. In this article we survey recent developments in Monte Carlo conditional analysis for log-linear and logistic models focusing on the algorithms proposed by Booth and Butler, Diaconis and Sturmfels, Smith et al., and Mehta et al. We illustrate these algorithms with simple motivating examples.