Intrathecal antibody distribution in the rat brain: surface diffusion, perivascular transport and osmotic enhancement of delivery.

KEY POINTS: It is unclear precisely how macromolecules (e.g. endogenous proteins and exogenous immunotherapeutics) access brain tissue from the cerebrospinal fluid (CSF). We show that transport at the brain-CSF interface involves a balance between Fickian diffusion in the extracellular spaces at the brain surface and convective transport in perivascular spaces of cerebral blood vessels. Intrathecally-infused antibodies exhibited size-dependent access to the perivascular spaces and tunica media basement membranes of leptomeningeal arteries. Perivascular access and distribution of full-length IgG could be enhanced by intrathecal co-infusion of hyperosmolar mannitol. Pores or stomata present on CSF-facing leptomeningeal cells ensheathing blood vessels in the subarachnoid space may provide unique entry sites into the perivascular spaces from the CSF. These results illuminate new mechanisms likely to govern antibody trafficking at the brain-CSF interface with relevance for immune surveillance in the healthy brain and insights into the distribution of therapeutic antibodies. ABSTRACT: The precise mechanisms governing the central distribution of macromolecules from the cerebrospinal fluid (CSF) to the brain and spinal cord remain poorly understood, despite their importance for physiological processes such as antibody trafficking for central immune surveillance, as well as several ongoing intrathecal clinical trials. In the present study, we clarify how IgG and smaller single-domain antibodies (sdAb) distribute throughout the whole brain in a size-dependent manner after intrathecal infusion in rats using ex vivo fluorescence and in vivo three-dimensional magnetic resonance imaging. Antibody distribution was characterized by diffusion at the brain surface and widespread distribution to deep brain regions along the perivascular spaces of all vessel types, with sdAb accessing a four- to seven-fold greater brain area than IgG. Perivascular transport involved blood vessels of all caliber and putative smooth muscle and astroglial basement membrane compartments. Perivascular access to smooth muscle basement membrane compartments also exhibited size-dependence. Electron microscopy was used to show stomata on leptomeningeal coverings of blood vessels in the subarachnoid space as potential access points allowing substances in the CSF to enter the perivascular space. Osmolyte co-infusion significantly enhanced perivascular access of the larger antibody from the CSF, with intrathecal 0.75 m mannitol increasing the number of perivascular profiles per slice area accessed by IgG by ∼50%. The results of the present study reveal potential distribution mechanisms for endogenous IgG, which is one of the most abundant proteins in the CSF, as well as provide new insights with respect to understanding and improving the drug delivery of macromolecules to the central nervous system via the intrathecal route.

Data-driven optimized flip angle selection for T1 estimation from spoiled gradient echo acquisitions.

PURPOSE: Define criteria for selection of optimal flip angle sets for T1 estimation and evaluate effects on T1 mapping. THEORY AND METHODS: Flip angle sets for spoiled gradient echo-based T1 mapping were selected by minimizing T1 estimate variance weighted by the joint density of M0 and T1 in an initial acquisition. The effect of optimized flip angle selection on T1 estimate error was measured using simulations and experimental data in the human and rat brain. RESULTS: For two-point acquisitions, optimized angle sets were similar to those proposed by other groups and, therefore, performed similarly. For multipoint acquisitions, optimal angle sets for T1 mapping in the brain consisted of a repetition of two angles. Implementation of optimal angles reduced T1 estimate variance by 30-40% compared with a multipoint acquisition using a range of angles. Performance of the optimal angle set was equivalent to that of a repetition of the two-angle set selected using criteria proposed by other researchers. CONCLUSION: Repetition of two carefully selected flip angles notably improves the precision of resulting T1 estimates compared with acquisitions using a range of flip angles. This work provides a flexible and widely applicable optimization method of particular use for those who repeatedly perform T1 estimation. Magn Reson Med 76:792-802, 2016. © 2015 Wiley Periodicals, Inc.

The effect of scan length on the reliability of resting-state fMRI connectivity estimates.

There has been an increasing use of functional magnetic resonance imaging (fMRI) by the neuroscience community to examine differences in functional connectivity between normal control groups and populations of interest. Understanding the reliability of these functional connections is essential to the study of neurological development and degenerate neuropathological conditions. To date, most research assessing the reliability with which resting-state functional connectivity characterizes the brain's functional networks has been on scans between 3 and 11 min in length. In our present study, we examine the test-retest reliability and similarity of resting-state functional connectivity for scans ranging in length from 3 to 27 min as well as for time series acquired during the same length of time but excluding half the time points via sampling every second image. Our results show that reliability and similarity can be greatly improved by increasing the scan lengths from 5 min up to 13 min, and that both the increase in the number of volumes as well as the increase in the length of time over which these volumes was acquired drove this increase in reliability. This improvement in reliability due to scan length is much greater for scans acquired during the same session. Gains in intersession reliability began to diminish after 9-12 min, while improvements in intrasession reliability plateaued around 12-16 min. Consequently, new techniques that improve reliability across sessions will be important for the interpretation of longitudinal fMRI studies.

Association of functional magnetic resonance imaging indices with postoperative language outcomes in patients with primary brain tumors.

OBJECT: Functional MRI (fMRI) has the potential to be a useful presurgical planning tool to treat patients with primary brain tumor. In this study the authors retrospectively explored relationships between language-related postoperative outcomes in such patients and multiple factors, including measures estimated from task fMRI maps (proximity of lesion to functional activation area, or lesion-to-activation distance [LAD], and activation-based language lateralization, or lateralization index [LI]) used in the clinical setting for presurgical planning, as well as other factors such as patient age, patient sex, tumor grade, and tumor volume. METHODS: Patient information was drawn from a database of patients with brain tumors who had undergone preoperative fMRI-based language mapping of the Broca and Wernicke areas. Patients had performed a battery of tasks, including word-generation tasks and a text-versus-symbols reading task, as part of a clinical fMRI protocol. Individually thresholded task fMRI activation maps had been provided for use in the clinical setting. These clinical imaging maps were used to retrospectively estimate LAD and LI for the Broca and Wernicke areas. RESULTS: There was a relationship between postoperative language deficits and the proximity between tumor and Broca area activation (the LAD estimate), where shorter LADs were related to the presence of postoperative aphasia. Stratification by tumor location further showed that for posterior tumors within the temporal and parietal lobes, more bilaterally oriented Broca area activation (LI estimate close to 0) and a shorter Wernicke area LAD were associated with increased postoperative aphasia. Furthermore, decreasing LAD was related to decreasing LI for both Broca and Wernicke areas. Preoperative deficits were related to increasing patient age and a shorter Wernicke area LAD. CONCLUSIONS: Overall, LAD and LI, as determined using fMRI in the context of these paradigms, may be useful indicators of postsurgical outcomes. Whereas tumor location may influence postoperative deficits, the results indicated that tumor proximity to an activation area might also interact with how the language network is affected as a whole by the lesion. Although the derivation of LI must be further validated in individual patients by using spatially specific statistical methods, the current results indicated that fMRI is a useful tool for predicting postoperative outcomes in patients with a single brain tumor.

Sparse and optimal acquisition design for diffusion MRI and beyond.

PURPOSE: Diffusion magnetic resonance imaging (MRI) in combination with functional MRI promises a whole new vista for scientists to investigate noninvasively the structural and functional connectivity of the human brain-the human connectome, which had heretofore been out of reach. As with other imaging modalities, diffusion MRI data are inherently noisy and its acquisition time-consuming. Further, a faithful representation of the human connectome that can serve as a predictive model requires a robust and accurate data-analytic pipeline. The focus of this paper is on one of the key segments of this pipeline-in particular, the development of a sparse and optimal acquisition (SOA) design for diffusion MRI multiple-shell acquisition and beyond. METHODS: The authors propose a novel optimality criterion for sparse multiple-shell acquisition and quasimultiple-shell designs in diffusion MRI and a novel and effective semistochastic and moderately greedy combinatorial search strategy with simulated annealing to locate the optimum design or configuration. The goal of the optimality criteria is threefold: first, to maximize uniformity of the diffusion measurements in each shell, which is equivalent to maximal incoherence in angular measurements; second, to maximize coverage of the diffusion measurements around each radial line to achieve maximal incoherence in radial measurements for multiple-shell acquisition; and finally, to ensure maximum uniformity of diffusion measurement directions in the limiting case when all the shells are coincidental as in the case of a single-shell acquisition. The approach taken in evaluating the stability of various acquisition designs is based on the condition number and the A-optimal measure of the design matrix. RESULTS: Even though the number of distinct configurations for a given set of diffusion gradient directions is very large in general-e.g., in the order of 10(232) for a set of 144 diffusion gradient directions, the proposed search strategy was found to be effective in finding the optimum configuration. It was found that the square design is the most robust (i.e., with stable condition numbers and A-optimal measures under varying experimental conditions) among many other possible designs of the same sample size. Under the same performance evaluation, the square design was found to be more robust than the widely used sampling schemes similar to that of 3D radial MRI and of diffusion spectrum imaging (DSI). CONCLUSIONS: A novel optimality criterion for sparse multiple-shell acquisition and quasimultiple-shell designs in diffusion MRI and an effective search strategy for finding the best configuration have been developed. The results are very promising, interesting, and practical for diffusion MRI acquisitions.

Extremely efficient and deterministic approach to generating optimal ordering of diffusion MRI measurements.

PURPOSE: Diffusion MRI measurements are typically acquired sequentially with unit gradient directions that are distributed uniformly on the unit sphere. The ordering of the gradient directions has significant effect on the quality of dMRI-derived quantities. Even though several methods have been proposed to generate optimal orderings of gradient directions, these methods are not widely used in clinical studies because of the two major problems. The first problem is that the existing methods for generating highly uniform and antipodally symmetric gradient directions are inefficient. The second problem is that the existing methods for generating optimal orderings of gradient directions are also highly inefficient. In this work, the authors propose two extremely efficient and deterministic methods to solve these two problems. METHODS: The method for generating nearly uniform point set on the unit sphere (with antipodal symmetry) is based upon the notion that the spacing between two consecutive points on the same latitude should be equal to the spacing between two consecutive latitudes. The method for generating optimal ordering of diffusion gradient directions is based on the idea that each subset of incremental sample size, which is derived from the prescribed and full set of gradient directions, must be as uniform as possible in terms of the modified electrostatic energy designed for antipodally symmetric point set. RESULTS: The proposed method outperformed the state-of-the-art method in terms of computational efficiency by about six orders of magnitude. CONCLUSIONS: Two extremely efficient and deterministic methods have been developed for solving the problem of optimal ordering of diffusion gradient directions. The proposed strategy is also applicable to optimal view-ordering in three-dimensional radial MRI.

Functional neuroimaging correlates of finger-tapping task variations: an ALE meta-analysis.

Finger-tapping tasks are one of the most common paradigms used to study the human motor system in functional neuroimaging studies. These tasks can vary both in the presence or absence of a pacing stimulus as well as in the complexity of the tapping task. A voxel-wise, coordinate-based meta-analysis was performed on 685 sets of activation foci in Talairach space gathered from 38 published studies employing finger-tapping tasks. Clusters of concordance were identified within the primary sensorimotor cortices, supplementary motor area, premotor cortex, inferior parietal cortices, basal ganglia, and anterior cerebellum. Subsequent analyses performed on subsets of the primary set of foci demonstrated that the use of a pacing stimulus resulted in a larger, more diverse network of concordance clusters, in comparison to varying the complexity of the tapping task. The majority of the additional concordance clusters occurred in regions involved in the temporal aspects of the tapping task, rather than its execution. Tapping tasks employing a visual pacing stimulus recruited a set of nodes distinct from the results observed in those tasks employing either an auditory or no pacing stimulus, suggesting differing cognitive networks when integrating visual or auditory pacing stimuli into simple motor tasks. The relatively uniform network of concordance clusters observed across the more complex finger-tapping tasks suggests that further complexity, beyond the use of multi-finger sequences or bimanual tasks, may be required to fully reveal those brain regions necessary to execute truly complex movements.

Childhood Emotional Abuse Moderates Associations Among Corticomotor White Matter Structure and Stress Neuromodulators in Women With and Without Depression.

Adverse caregiving during development can produce long-lasting changes to neural, endocrine, and behavioral responses to stress, and is strongly related to elevated risk of adult psychopathology. While prior experience of adversity is associated with altered sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis activity, the underlying neural pathways are not completely understood. In a double-blind crossover study, we used diffusion tensor imaging (DTI) to examine whether variation in white matter structure predicts differences in HPA-SNS interactions as a function of early adversity. Participants included 74 women who exhibited a wide range of depression severity and/or childhood emotional abuse (EA). Participants attended two experimental sessions during which they were administered 20 mg cortisol (CORT) or placebo and after 90 min, viewed emotionally laden pictures while undergoing MRI scanning. Immediately after emotional picture-viewing, we collected salivary alpha-amylase (sAA) to index SNS activation. We tested whether EA moderated the relation between fractional anisotropy (FA), a measure of white matter fiber structure, and sAA. In the placebo condition, for participants with minimal history of EA, higher FA in corticomotor projections was negatively correlated with sAA, whereas in participants with severe EA, the correlation was trending in the opposite direction. Following CORT administration, FA and sAA were not related, suggesting that SNS tone during acute cortisol elevation may depend on neural pathways other than corticomotor projections. The results suggest that at baseline-though not during cortisol elevation-increased FA in these tracts is associated with lower levels of SNS activity in women with minimal EA, but not in women with severe EA. These findings provide evidence that corticomotor projections may be a key component of altered neural circuitry in adults with history of maltreatment, and may be related to alterations in stress neuromodulators in psychopathology.

Self-paced working memory: validation of verbal variations of the n-back paradigm.

Self-paced versions of many paradigms could have utility in probing cognitive systems. To validate several self-paced n-back paradigms, fourteen subjects performed four variations of the working memory task using visually presented letters as stimuli. Several areas in the frontal lobe, the anterior cingulate and a parietal network were consistently activated in the four variations: identity of black letters, location of black letters, color of colored letters and identity of colored letters. Since the n-back task is one of the more popular methods of investigating working memory, we validated the utility of several self-paced versions in normal subjects via quantitative, coordinate-based meta-analyses. The self-paced results agree well with meta-analyses and other published results, giving confidence that a self-paced n-back paradigm is robust in multiple variations. Behavioral results differ from other published reports, perhaps offering insight into true working memory strategy in normal subjects.

An objective method for combining multi-parametric MRI datasets to characterize malignant tumors.

Medical imaging has made significant contributions to the characterization of malignant tumors. In many cases, however, maps from multiple modalities may be required for more complete tumor mapping. In this manuscript we propose an objective method for combining multiple imaging datasets with the goal of characterizing malignant tumors. We refer to the proposed technique as the percent overlap method (POM). To demonstrate the power and flexibility of the POM analysis, we present four patients with recurrent glioblastoma multiforme. Each patient had multiple magnetic resonance imaging procedures resulting in seven different parameter maps. Chemical shift imaging was used to provide three metabolite ratio maps (Cho:NAA, Cho:Cre, Lac:Cre). A perfusion scan provided regional cerebral blood volume and permeability maps. Diffusion and carbogen-based hypoxia mapping data were also acquired. Composite maps were formed for each patient using POM, then were compared to results from the ISODATA clustering technique. The POM maps of likely recurrent tumor regions were found to be consistent with the ISODATA clustering method. This manuscript presents an objective method for combining parameters from multiple physiologic imaging techniques into a single composite map. The accuracy of the map depends strongly on the sensitivity of the chosen imaging parameters to the disease process at the time of image acquisition. Further validation of this method may be achieved by correlation with histological data.

Challenges and Opportunities: Building a Relationship Between a Department of Biomedical Engineering and a Medical School.

A department of biomedical engineering can significantly enhance the impact of their research and training programs if a productive relationship with a medical school can be established. In order to develop such a relationship, significant hurdles must be overcome. This editorial summarizes some of the major challenges and opportunities for a department of biomedical engineering as they seek to build or enhance a relationship with a medical school. The ideas were formulated by engaging the collective wisdom from the Council of Chairs of the biomedical engineering departments.

The Impact of Intracranial Tumor Proximity to White Matter Tracts on Morbidity and Mortality: A Retrospective Diffusion Tensor Imaging Study.

Background: Using diffusion tensor imaging (DTI) in neurosurgical planning allows identification of white matter tracts and has been associated with a reduction in postoperative functional deficits. Objective: This study explores the relationship between the lesion-to-tract distance (LTD) and postoperative morbidity and mortality in patients with brain tumors in order to evaluate the role of DTI in predicting postoperative outcomes. Methods: Adult patients with brain tumors (n = 60) underwent preoperative DTI. Three major white matter pathways (superior longitudinal fasciculi [SLF], cingulum, and corticospinal tract) were identified using DTI images, and the shortest LTD was measured for each tract. Postoperative morbidity and mortality information was collected from electronic medical records. Results: The ipsilesional corticospinal tract LTD and left SLF LTD were significantly associated with the occurrence rate of total postoperative motor (P = .018) and language (P < .001) deficits, respectively. The left SLF LTD was also significantly associated with the occurrence rate of new postoperative language deficits (P = .003), and the LTD threshold that best predicted this occurrence was 1 cm (P < .001). Kaplan­Meier log-rank survival analyses in patients having high-grade tumors demonstrated a significantly higher mortality for patients with a left SLF LTD <1 cm (P = .01). Conclusion: Measuring tumor proximity to major white matter tracts using DTI can inform clinicians of the likelihood of postoperative functional deficits. A distance of 1 cm or less from eloquent white matter structures most significantly predicts the occurrence of new deficits with current surgical and imaging techniques.

Physiologic characterisation of glioblastoma multiforme using MRI-based hypoxia mapping, chemical shift imaging, perfusion and diffusion maps.

PURPOSE: A multiparametric, physiologic MRI approach was considered to more completely characterise biopsy-confirmed glioblastoma multiforme (GBM). Chemical shift imaging (CSI) supplied biochemical information in metabolite ratios, while perfusion images provided data on presumed vascularity from regional cerebral blood volume (rCBV) and permeability maps. Diffusion-weighted images were reduced to apparent diffusion coefficient (ADC) maps to evaluate cellularity, and blood oxygen level-dependent imaging was used to create maps of putative hypoxic regions. METHODS: Six post-treatment GBM patients were scanned at 3-month intervals until recurrence was suggested by conventional MRI parameters, yielding 20 scans for consideration. The percentage of extreme values in each technique that overlapped with other parameters was measured and compared across hemispheres to assess utility. RESULTS: We found significantly better performance in selecting the diseased hemisphere for overall percent overlap when compared to voxel counts from individual thresholded parameter maps. Parameters were selected on the basis of highest overlap, and corresponding composite overlap maps show increased specificity to likely recurrent regions by reducing the number of falsely positive voxels, and offer insight into relationships between various parameters. CONCLUSION: In a pilot group of patients, percent overlap appears to be sensitive to recurrent disease. When used to combine multiple parameters, voxels containing overlap can specifically target probable recurrent areas.

Classification and Extraction of Resting State Networks Using Healthy and Epilepsy fMRI Data.

Functional magnetic resonance imaging studies have significantly expanded the field's understanding of functional brain activity of healthy and patient populations. Resting state (rs-) fMRI, which does not require subjects to perform a task, eliminating confounds of task difficulty, allows examination of neural activity and offers valuable functional mapping information. The purpose of this work was to develop an automatic resting state network (RSN) labeling method which offers value in clinical workflow during rs-fMRI mapping by organizing and quickly labeling spatial maps into functional networks. Here independent component analysis (ICA) and machine learning were applied to rs-fMRI data with the goal of developing a method for the clinically oriented task of extracting and classifying spatial maps into auditory, visual, default-mode, sensorimotor, and executive control RSNs from 23 epilepsy patients (and for general comparison, separately for 30 healthy subjects). ICA revealed distinct and consistent functional network components across patients and healthy subjects. Network classification was successful, achieving 88% accuracy for epilepsy patients with a naïve Bayes algorithm (and 90% accuracy for healthy subjects with a perceptron). The method's utility to researchers and clinicians is the provided RSN spatial maps and their functional labeling which offer complementary functional information to clinicians' expert interpretation.

In Vivo Tracking of Human Neural Progenitor Cells in the Rat Brain Using Magnetic Resonance Imaging Is Not Enhanced by Ferritin Expression.

Rapid growth in the field of stem cell research has generated a lot of interest in their therapeutic use, especially in the treatment of neurodegenerative diseases. Specifically, human neural progenitor cells (hNPCs), unique in their capability to differentiate into cells of the neural lineage, have been widely investigated due to their ability to survive, thrive, and migrate toward injured tissues. Still, one of the major roadblocks for clinical applicability arises from the inability to monitor these cells following transplantation. Molecular imaging techniques, such as magnetic resonance imaging (MRI), have been explored to assess hNPC transplant location, migration, and survival. Here we investigated whether inducing hNPCs to overexpress ferritin (hNPCs(Fer)), an iron storage protein, is sufficient to track these cells long term in the rat striatum using MRI. We found that increased hypointensity on MRI images could establish hNPC(Fer) location. Unexpectedly, however, wild-type hNPC transplants were detected in a similar manner, which is likely due to increased iron accumulation following transplantation-induced damage. Hence, we labeled hNPCs with superparamagnetic iron oxide (SPIO) nanoparticles to further increase iron content in an attempt to enhance cell contrast in MRI. SPIO-labeling of hNPCs (hNPCs-SPIO) achieved increased hypointensity, with significantly greater area of decreased T2* compared to hNPC(Fer) (p < 0.0001) and all other controls used. However, none of the techniques could be used to determine graft rejection in vivo, which is imperative for understanding cell behavior following transplantation. We conclude that in order for cell survival to be monitored in preclinical and clinical settings, another molecular imaging technique must be employed, including perhaps multimodal imaging, which would utilize MRI along with another imaging modality.

Uptake and retention of manganese contrast agents for PET and MRI in the rodent brain.

Manganese-enhanced magnetic resonance imaging (MRI) is an established neuroimaging method for signal enhancement, tract tracing, and functional studies in rodents. Along with the increasing availability of combined positron emission tomography (PET) and MRI scanners, the recent development of the positron-emitting isotope 52 Mn has prompted interest in the use of Mn2+ as a dual-modality contrast agent. In this work, we characterized and compared the uptake of systemically delivered Mn2+ and radioactive 52 Mn2+ in the rat brain for MRI and PET, respectively. Additionally, we examined the biodistribution of two formulations of 52 Mn2+ in the rat. In MRI, maximum uptake was observed one day following delivery of the highest MnCl2 dose tested (60 mg/kg), with some brain regions showing delayed maximum enhancement 2-4 days following delivery. In PET, we observed low brain uptake after systemic delivery, with a maximum of approximately 0.2% ID/g. We also studied the effect of final formulation vehicle (saline compared with MnCl2 ) on 52 Mn2+ organ biodistribution and brain uptake. We observed that the addition of bulk Mn2+ carrier to 52 Mn2+ in solution resulted in significantly reduced 52 Mn2+ uptake in the majority of organs, including the brain. These results lay the groundwork for further development of 52 Mn PET or dual Mn-enhanced PET-MR neuroimaging in rodents, and indicate several interesting potential applications of 52 Mn PET in other organs and systems. Copyright © 2016 John Wiley & Sons, Ltd.

Usage of fMRI for pre-surgical planning in brain tumor and vascular lesion patients: task and statistical threshold effects on language lateralization.

BACKGROUND AND PURPOSE: Functional magnetic resonance imaging (fMRI) is a non-invasive pre-surgical tool used to assess localization and lateralization of language function in brain tumor and vascular lesion patients in order to guide neurosurgeons as they devise a surgical approach to treat these lesions. We investigated the effect of varying the statistical thresholds as well as the type of language tasks on functional activation patterns and language lateralization. We hypothesized that language lateralization indices (LIs) would be threshold- and task-dependent. MATERIALS AND METHODS: Imaging data were collected from brain tumor patients (n = 67, average age 48 years) and vascular lesion patients (n = 25, average age 43 years) who received pre-operative fMRI scanning. Both patient groups performed expressive (antonym and/or letter-word generation) and receptive (tumor patients performed text-reading; vascular lesion patients performed text-listening) language tasks. A control group (n = 25, average age 45 years) performed the letter-word generation task. RESULTS: Brain tumor patients showed left-lateralization during the antonym-word generation and text-reading tasks at high threshold values and bilateral activation during the letter-word generation task, irrespective of the threshold values. Vascular lesion patients showed left-lateralization during the antonym and letter-word generation, and text-listening tasks at high threshold values. CONCLUSION: Our results suggest that the type of task and the applied statistical threshold influence LI and that the threshold effects on LI may be task-specific. Thus identifying critical functional regions and computing LIs should be conducted on an individual subject basis, using a continuum of threshold values with different tasks to provide the most accurate information for surgical planning to minimize post-operative language deficits.

Measuring the axial rotation of lumbar vertebrae in vivo with MR imaging.

BACKGROUND AND PURPOSE: Flexion-extension radiography is neither sensitive nor specific in the diagnosis of degenerative spinal instability, a presumed cause of back pain and an indication for spinal fusion. We tested the hypothesis that with MR imaging and a device to rotate the torso, axial rotations of lumbar vertebrae can be measured with sufficient accuracy and that significantly different rotations can be detected between lumbar segments with degenerated disks and those with normal disks. METHODS: We studied five volunteers without back pain (group 1), five patients who underwent MR imaging because of back pain but were not considered candidates for fusion (group 2), and five patients in whom diskography identified one or more disks with concordant pain (group 3). Each participant was placed on a specially built table that provided separate supports for the torso and for the hips and legs. Series of sagittal images were acquired with a T2-weighted fast spin-echo sequence, with the torso rotated clockwise and then counterclockwise. The amount of rotation was calculated from axial images with use of an automated program. RESULTS: In the five volunteers, rotations of the lumbar motion segments varied between -1.8 degrees and 5.7 degrees, with an average of 0.8 degrees. The abnormal disks in five patients in group 2 rotated from -0.9 degrees to 5.6 degrees, with an average of 3.2 degrees. In group 3, the disks in which concordant pain was elicited rotated from 0.8 degrees to 4.4 degrees, with an average of 2.2 degrees. Difference in rotation between abnormal and normal disks was statistically significant. CONCLUSION: Measurements of rotations of lumbar vertebrae with MR imaging may have value for determining levels that move abnormally in axial rotation.

Role of the corpus callosum in functional connectivity.

BACKGROUND AND PURPOSE: Regional cerebral blood flow fluctuates synchronously in corresponding brain regions between the hemispheres. This synchrony implies neuronal connections between brain regions. The synchrony of blood flow changes is defined operationally as functional connectivity. Our purpose was to measure functional connectivity in patients with corpus callosal agenesis, in whom the interhemispheric connectivity is hypothetically diminished. METHODS: In three patients with agenesis of the corpus callosum, functional MR imaging was performed while patients performed text-listening and finger-tapping tasks. Functional images were also acquired while the patients performed no specific task (resting state). Regions of activation temporally correlated with the performance of the tasks were identified by cross-correlating the task data with a reference function. Voxel clusters (seed voxels) that corresponded to regions of activation in the task-activation data set were selected in the resting data set. All the voxels in the resting 3D data set that had a correlation coefficient exceeding 0.4 were identified. The number of these voxels in the ipsilateral and contralateral hemispheres was tabulated. RESULTS: In all patients, technically adequate functional MR and functional connectivity MR maps were obtained. For both tasks, activation was found in both hemispheres. For all of the seed voxels, significantly more functionally connected voxels were found in the ipsilateral hemisphere than in the contralateral hemisphere. For most seed voxels, no functionally connected voxels were found in the contralateral hemisphere. CONCLUSION: Interhemispheric functional connectivity in the motor and auditory cortices is diminished in patients with agenesis of the corpus callosum compared with that of healthy subjects.