G. Bruce Pike

Stereotaxic White Matter Atlas Based on Diffusion Tensor Imaging in an ICBM Template

Brain registration to a stereotaxic atlas is an effective way to report anatomic locations of interest and to perform anatomic quantification. However, existing stereotaxic atlases lack comprehensive coordinate information about white matter structures. In this paper, white matter-specific atlases in stereotaxic coordinates are introduced. As a reference template, the widely used ICBM-152 was used. The atlas contains fiber orientation maps and hand-segmented white matter parcellation maps based on diffusion tensor imaging (DTI). Registration accuracy by linear and non-linear transformation was measured, and automated template-based white matter parcellation was tested. The results showed a high correlation between the manual ROI-based and the automated approaches for normal adult populations. The atlases are freely available and believed to be a useful resource as a target template and for automated parcellation methods.

Investigation of BOLD Signal Dependence on Cerebral Blood Flow and Oxygen Consumption: The Deoxyhemoglobin Dilution Model

The relationship between blood oxygenation level‐dependent (BOLD) MRI signals, cerebral blood flow (CBF), and oxygen consumption (CMRO2) in the physiological steady state was investigated. A quantitative model, based on flow‐dependent dilution of metabolically generated deoxyhemoglobin, was validated by measuring BOLD signals and relative CBF simultaneously in the primary visual cortex (V1) of human subjects (N = 12) during graded hypercapnia at different levels of visual stimulation. BOLD and CBF responses to specific conditions were averaged across subjects and plotted as points in the BOLD‐CBF plane, tracing out lines of constant CMRO2. The quantitative deoxyhemoglobin dilution model could be fit to these measured iso‐CMRO2 contours without significant (P ≤ 0.05) residual error and yielded MRI‐based CMRO2 measurements that were in agreement with PET results for equivalent stimuli. BOLD and CBF data acquired during graded visual stimulation were then substituted into the model with constant parameters varied over plausible ranges. Relative changes in CBF and CMRO2 appeared to be coupled in an approximate ratio of ∼2:1 for all realistic parameter settings. Magn Reson Med 42:849–863, 1999.

Dissociating the Human Language Pathways with High Angular Resolution Diffusion Fiber Tractography

The anatomical connectivity of ventrolateral frontal areas 44 and 45, which in the human brain constitute Brocas region, has been revisited on the basis of experimental anatomical tracer evidence in the nonhuman primate that the homologues of areas 44 and 45 have distinct bidirectional corticocortical connections. Here we show, using high angular resolution diffusion imaging in the living human brain, a dissociation between the specific projections from the pars opercularis (area 44) and the pars triangularis (area 45) in the ventrolateral frontal lobe. As in the macaque monkey, area 44 has distinct connections with the rostral inferior parietal lobule via the third branch of the superior longitudinal fasciculus. In contrast, area 45 connects with the superior temporal gyrus, anterior to Heschls gyrus, via the extreme capsule fiber system. These results highlight the differences in connectivity between areas 44 and 45 which had previously been thought to be uniformly connected with the posterior temporal region via the arcuate fasciculus. We also provide evidence in the human brain that the arcuate fasciculus, as in the macaque monkey brain, connects the posterior superior temporal region with dorsolateral frontal areas 8 and rostral 6 that lie above areas 44 and 45. Thus, monkey and human evidence suggests that the connections of areas 44 and 45 are much more differentiated than had previously been thought and provide the basis for studies searching for their differential contribution in function.

Quantitative imaging of magnetization transfer exchange and relaxation properties in vivo using MRI

We describe a novel imaging technique that yields all of the observable properties of the binary spin‐bath model for magnetization transfer (MT) and demonstrate this method for in vivo studies of the human head. Based on a new model of the steady‐state behavior of the magnetization during a pulsed MT‐weighted imaging sequence, this approach yields parametric images of the fractional size of the restricted pool, the magnetization exchange rate, the T2 of the restricted pool, as well as the relaxation times in the free pool. Validated experimentally on agar gels and samples of uncooked beef, we demonstrate the methods application on two normal subjects and a patient with multiple sclerosis. Magn Reson Med 46:923–931, 2001.

Human Brain White Matter Atlas: Identification and Assignment of Common Anatomical Structures in Superficial White Matter

Structural delineation and assignment are the fundamental steps in understanding the anatomy of the human brain. The white matter has been structurally defined in the past only at its core regions (deep white matter). However, the most peripheral white matter areas, which are interleaved between the cortex and the deep white matter, have lacked clear anatomical definitions and parcellations. We used axonal fiber alignment information from diffusion tensor imaging (DTI) to delineate the peripheral white matter, and investigated its relationship with the cortex and the deep white matter. Using DTI data from 81 healthy subjects, we identified nine common, blade-like anatomical regions, which were further parcellated into 21 subregions based on the cortical anatomy. Four short association fiber tracts connecting adjacent gyri (U-fibers) were also identified reproducibly among the healthy population. We anticipate that this atlas will be useful resource for atlas-based white matter anatomical studies.

Hemodynamic and metabolic responses to neuronal inhibition

Functional magnetic resonance imaging (fMRI) was used to investigate the changes in blood oxygenation level dependent (BOLD) signal, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMR(O(2))) accompanying neuronal inhibition. Eight healthy volunteers performed a periodic right-hand pinch grip every second using 5% of their maximum voluntary contraction (MVC), a paradigm previously shown to produce robust ipsilateral neuronal inhibition. To simultaneously quantify CBF and BOLD signals, an interleaved multislice pulsed arterial spin labeling (PASL) and T(2)*-weighted gradient echo sequence was employed. The CMR(O(2)) was calculated using the deoxyhemoglobin dilution model, calibrated by data measured during graded hypercapnia. In all subjects, BOLD, CBF and CMR(O(2)) signals increased in the contralateral and decreased in the ipsilateral primary motor (M1) cortex. The relative changes in CMR(O(2)) and CBF were linearly related, with a slope of approximately 0.4. The coupling ratio thus established for both positive and negative CMR(O(2)) and CBF changes is in close agreement with the ones observed by earlier studies investigating M1 perfusion and oxygen consumption increases. These findings characterize the hemodynamic and metabolic downregulation accompanying neuronal inhibition and thereby establish the sustained negative BOLD response as a marker of neuronal deactivation.

An Extensible MRI Simulator for Post-Processing Evaluation

An extensible object-oriented MRI simulation system is presented. This simulator uses first-principle modelling based on the Bloch equations to implement a discrete-event simulation of NMR signal production. A model of the image production process, incorporating noise and partial volume effects, has also been developed based on first-principles. This is used to generate realistic simulated MRI volumes, based on a labelled data set, for the evaluation of classification algorithms and other post-processing routines.

Growth of White Matter in the Adolescent Brain: Role of Testosterone and Androgen Receptor

The growth of white matter during human adolescence shows a striking sexual dimorphism; the volume of white matter increases with age slightly in girls and steeply in boys. Here, we provide evidence supporting the role of androgen receptor (AR) in mediating the effect of testosterone on white matter. In a large sample of typically developing adolescents (n = 408, 204 males), we used magnetic resonance imaging and acquired T1-weighted and magnetization transfer ratio (MTR) images. We also measured plasma levels of testosterone and genotyped a functional polymorphism in the AR gene, namely the number of CAG repeats in exon 1 believed to be inversely proportional to the AR transcriptional activity. We found that the testosterone-related increase of white-matter volume was stronger in male adolescents with the lower versus higher number of CAG repeats in the AR gene, with testosterone explaining, respectively, 26 and 8% of variance in the volume. The MTR results suggest that this growth is not related to myelination; the MTR decreased with age in male adolescents. We speculate that testosterone affects axonal caliber rather than the thickness of the myelin sheath.

EEG-fMRI of focal epileptic spikes: Analysis with multiple haemodynamic functions and comparison with gadolinium-enhanced MR angiograms

Combined EEG‐fMRI has recently been used to explore the BOLD responses to interictal epileptiform discharges. This study examines whether misspecification of the form of the haemodynamic response function (HRF) results in significant fMRI responses being missed in the statistical analysis. EEG‐fMRI data from 31 patients with focal epilepsy were analysed with four HRFs peaking from 3 to 9 sec after each interictal event, in addition to a standard HRF that peaked after 5.4 sec. In four patients, fMRI responses were correlated with gadolinium‐enhanced MR angiograms and with EEG data from intracranial electrodes. In an attempt to understand the absence of BOLD responses in a significant group of patients, the degree of signal loss occurring as a result of magnetic field inhomogeneities was compared with the detected fMRI responses in ten patients with temporal lobe spikes. Using multiple HRFs resulted in an increased percentage of data sets with significant fMRI activations, from 45% when using the standard HRF alone, to 62.5%. The standard HRF was good at detecting positive BOLD responses, but less appropriate for negative BOLD responses, the majority of which were more accurately modelled by an HRF that peaked later than the standard. Co‐registration of statistical maps with gadolinium‐enhanced MRIs suggested that the detected fMRI responses were not in general related to large veins. Signal loss in the temporal lobes seemed to be an important factor in 7 of 12 patients who did not show fMRI activations with any of the HRFs. Hum. Brain Mapp. 22:179–192, 2004.

Atlas-guided tract reconstruction for automated and comprehensive examination of the white matter anatomy

Tractography based on diffusion tensor imaging (DTI) is widely used to quantitatively analyze the status of the white matter anatomy in a tract-specific manner in many types of diseases. This approach, however, involves subjective judgment in the tract-editing process to extract only the tracts of interest. This process, usually performed by manual delineation of regions of interest, is also time-consuming, and certain tracts, especially the short cortico-cortical association fibers, are difficult to reconstruct. In this paper, we propose an automated approach for reconstruction of a large number of white matter tracts. In this approach, existing anatomical knowledge about tract trajectories (called the Template ROI Set or TRS) were stored in our DTI-based brain atlas with 130 three-dimensional anatomical segmentations, which were warped non-linearly to individual DTI data. We examined the degree of matching with manual results for selected fibers. We established 30 TRSs to reconstruct 30 prominent and previously well-described fibers. In addition, TRSs were developed to delineate 29 short association fibers that were found in all normal subjects examined in this paper (N=20). Probabilistic maps of the 59 tract trajectories were created from the normal subjects and were incorporated into our image analysis tool for automated tract-specific quantification.