Biomedical subjects

Claudia A M Wheeler-Kingshott

Publications and source records attributed to Claudia A M Wheeler-Kingshott.

16 recordsLinked to original sources

PubMed2006

Hemispheric asymmetries in language-related pathways: a combined functional MRI and tractography study.

Functional lateralization is a feature of human brain function, most apparent in the typical left-hemisphere specialization for language. A number of anatomical and imaging studies have examined whether structural asymmetries underlie this functional lateralization. We combined functional MRI (fMRI) and diffusion-weighted imaging (DWI) with tractography to study 10 healthy right-handed subjects. Three language fMRI paradigms were used to define language-related regions in inferior frontal and superior temporal regions. A probabilistic tractography technique was then employed to delineate the connections of these functionally defined regions. We demonstrated consistent connections between Broca's and Wernicke's areas along the superior longitudinal fasciculus bilaterally but more extensive fronto-temporal connectivity on the left than the right. Both tract volumes and mean fractional anisotropy (FA) were significantly greater on the left than the right. We also demonstrated a correlation between measures of structure and function, with subjects with more lateralized fMRI activation having a more highly lateralized mean FA of their connections. These structural asymmetries are in keeping with the lateralization of language function and indicate the major structural connections underlying this function.

Adult↗

PubMed2005

A simple correction for B1 field errors in magnetization transfer ratio measurements.

B1 errors are a problem in magnetization transfer ratio (MTR) measurements because the MTR value is dependent on the amplitude of the magnetization transfer (MT) pulse. B1 errors can arise from radiofrequency (RF) nonuniformity (caused by the RF coil, or skin effect and dielectric resonance in the subject's head) and also from inaccurate setting of the transmitter output when compensating for varying amounts of loading of the RF coil. B1 errors, and hence MTR errors, may be up to 5-10%, a large source of error in quantitative MR measurements. Radiofrequency nonuniformity may cause MTR histograms to be broadened. The dependence of MTR on B1 was modeled using binary spin bath theory, with a continuous wave (CW) approximation. For B1 reductions of up to 20%, normalized plots for different brain tissue types could be approximated by a single line, indicating that a systematic correction could be applied to MTR measurements with a known B1 error, regardless of tissue type. On a 1.5-T scanner with a birdcage coil, MTR was measured in 18 tissue types in five controls. The MT pulse amplitude was reduced in steps from its nominal value by up to 20%. Averaging data over all controls and tissue types resulted in a line fitting mtr(normalized)=0.812b(1normalized)+0.193, where mtr(normalized) is the normalized value of MTR (relative to its value at the nominal B1) and b(1normalized) is the normalized value of B1 (relative to its nominal value). For a 20% reduction in MT pulse amplitude (i.e., b(1normalized)=0.80), the mean MTR value for the 18 tissue types was 7.0 percent units (pu) below the correct value. After correction using the single equation above for all tissue types, all MTR values were within 1.5 pu of their correct value [root mean square (rms) error=0.7 pu]. Magnetization transfer ratio values tended to be slightly overcorrected because the simple linear correction scheme is only an approximation to the true MTR dependence on B1. A B1 field mapping technique was implemented, based on the double angle method (DAM), with fast spin-echo (FSE) readout, and TR=15 s; this took a total of 6 min of imaging time. This was used to quantify B(1) errors and correct MTR maps and histograms. However, the cerebrospinal fluid (CSF) T1 is very long (approximately 4.2 s); thus, to achieve complete longitudinal relaxation (a requirement of the DAM B1 mapping method), an increase in TR and, hence, acquisition time would be required. In general, however, we are not interested in calculating the B1 in the CSF, although it is important that the B1 is determined in partial volume voxels around the CSF. Using our birdcage head coil, whole-brain B1 histograms were found to have full-width half maximums (FWHMs) ranging from just 6.8% to 11.5% of the nominal B1 value. The FSE DAM B1 field mapping technique was shown to be robust, although a longer TR time may be desirable to ensure complete elimination of CSF partial volume errors. The procedure can be applied on any scanner where the Euro-MT sequence is available, or alternatively, where the amplitude of B1 or of the MT pulse can be manually reduced in order to perform this type of "calibration" experiment for the particular MTR sequence used. The MTR is known to be highly dependent on the parameters of the sequence used, in particular, the MT pulse shape, flip angle, duration, and offset frequency, and the repetition time TR' between successive MT pulses. Therefore, correction schemes will differ for different MTR sequences, and new data sets would be required to calculate these different correction schemes.

Algorithms↗

PubMed2005

Optic radiation changes after optic neuritis detected by tractography-based group mapping.

Postmortem data suggest that trans-synaptic degeneration occurs in the lateral geniculate nucleus after optic nerve injury. This study investigated in vivo the optic radiations in patients affected by optic neuritis using fast marching tractography (FMT), a diffusion magnetic resonance imaging (MRI) fiber tracking method, and group mapping techniques, which allow statistical comparisons between subjects. Seven patients, 1 year after isolated unilateral optic neuritis, and ten age and gender-matched controls underwent whole-brain diffusion tensor MR imaging. The FMT algorithm was used to generate voxel-scale connectivity (VSC) maps in the optic radiations in each subject in native space. Group maps of the left and right optic radiations were created in the patient and control group in a standardized reference frame using statistical parametric mapping (SPM99). The reconstructed optic radiations in the patient group were localized more laterally in the posterior part of the tracts and more inferiorly than in the control group. Patients showed reduced VSC values in both tracts compared with controls. These findings suggest that the group mapping techniques might be used to assess changes in the optic radiations in patients after an episode of optic neuritis. The changes we have observed may be secondary to the optic nerve damage.

Adult↗

PubMed2005

Postictal diffusion tensor imaging.

The objective of the study was to investigate postictal diffusion tensor imaging (DTI) in focal epilepsy. DTI and statistical parametric mapping (SPM) were used to examine objectively the diffusion properties of the brains of 18 patients with intractable focal epilepsy both postictally and interictally and to compare them with 27 normal controls scanned twice. Three sets of statistical tests were performed on each patient's fractional anisotropy and mean diffusivity data: interictal versus controls, postictal versus controls and a third "difference analysis" to test for significant changes in comparison with the differences noted between the two sets of control scans. Thirteen of the 18 patients (72%) had significant increases in mean diffusivity in the interictal scan. No decreases in mean diffusivity were detected. The difference analysis detected significant relative decreases in mean diffusivity postictally in nine patients (50%). These changes were focal in seven patients. In six of these, the site of the epileptic focus was known and co-localized with the diffusivity change in three. No significant changes in anisotropy were noted between the post- and interictal states. The postictal decrease in diffusivity probably reflects cellular swelling in the area of seizure onset and possibly areas of seizure spread. Postictal diffusivity changes appear complex and dynamic and timing after the seizure may be critical. Anisotropy measures appear less sensitive to these changes. Further systematic studies are needed and correlation with outcome after epilepsy surgery will determine the role of postictal diffusion measures in the presurgical evaluation of epilepsy patients.

Adult↗

PubMed2005

Optic nerve diffusion measurement from diffusion-weighted imaging in optic neuritis.

BACKGROUND AND PURPOSE: Increases in apparent diffusion coefficient (ADC) from diffusion-weighted (DW) imaging are thought to be due to axonal disruption, and changes have been well documented in multiple sclerosis lesions. DW imaging of the optic nerves, however, presents many challenges. The goal of this study was to measure ADC in patients with optic neuritis by using zonal oblique multisection echoplanar imaging. METHODS: The optic nerves of eighteen patients who had experienced an attack of optic neuritis 1 year previously and 11 control subjects were imaged with the diffusion sequence (usable data were available from 16 patients and 10 control subjects). The orbital optic nerves were segmented by a blinded observer by using a computer-assisted threshold-based contouring technique, and the mean ADC was determined. RESULTS: The mean ADC from diseased optic nerves was 1324 x 10(-6) mm2/s, compared with 990 x 10(-6) mm2/s from healthy contralateral optic nerves (P = .005 versus diseased optic nerves) and 928 x 10(-6) mm2/s from control optic nerves (P = .006 versus diseased optic nerves and P = .40 versus healthy contralateral optic nerves). The diseased optic nerve ADC correlated with both visual (e.g., r(S) = 0.73; P = .001 for logMAR visual acuity) and electrophysiological parameters (e.g., r(S) = -0.57, P = .021 for visual evoked potential central field amplitude [VEP]). CONCLUSION: It has been possible to apply DW imaging in a patient population, and, in the chronic phase following optic neuritis, the correlation of mean ADC with the clinical and electrophysiological parameters suggests that the ADC is giving a surrogate measure of axonal disruption in the chronic, postinflammatory optic nerve lesion.

Adult↗

PubMed2004

Lateralization of ventral and dorsal auditory-language pathways in the human brain.

Recent electrophysiological investigations of the auditory system in primates along with functional neuroimaging studies of auditory perception in humans have suggested there are two pathways arising from the primary auditory cortex. In the primate brain, a 'ventral' pathway is thought to project anteriorly from the primary auditory cortex to prefrontal areas along the superior temporal gyrus while a separate 'dorsal' route connects these areas posteriorly via the inferior parietal lobe. We use diffusion MRI tractography, a noninvasive technique based on diffusion-weighted MRI, to investigate the possibility of a similar pattern of connectivity in the human brain for the first time. The dorsal pathway from Wernicke's area to Broca's area is shown to include the arcuate fasciculus and connectivity to Brodmann area 40, lateral superior temporal gyrus (LSTG), and lateral middle temporal gyrus. A ventral route between Wernicke's area and Broca's area is demonstrated that connects via the external capsule/uncinate fasciculus and the medial superior temporal gyrus. Ventral connections are also observed in the lateral superior and middle temporal gyri. The connections are stronger in the dominant hemisphere, in agreement with previous studies of functional lateralization of auditory-language processing.

Adult↗

PubMed2004

Characterizing function-structure relationships in the human visual system with functional MRI and diffusion tensor imaging.

A key objective in neuroscience is to improve our understanding of the relationship between brain function and structure. We investigated this in the posterior visual pathways of healthy volunteers by applying functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) with tractography. The optic radiations were segmented using the Probabilistic Index of Connectivity (PICo) tractography algorithm and extracted at several thresholds of connection confidence. The mean fractional anisotropy (FA) of the estimated tracts was found to correlate significantly with fMRI measures of visual cortex activity (induced by a photic stimulation paradigm). The results support the hypothesis that the visual cortical fMRI response is constrained by the external anatomical connections of the subserving optic radiations.

Adult↗

PubMed2003

Reproducibility of brain ADC histograms.

The aim of this study was to assess the effect of differences in acquisition technique on whole-brain apparent diffusion coefficient (ADC) histogram parameters, as well as to assess scan-rescan reproducibility. Diffusion-weighted imaging (DWI) was performed in 7 healthy subjects with b-values 0-800, 0-1000, and 0-1500 s/mm(2) and fluid-attenuated inversion recovery (FLAIR) DWI with b-values 0-1000 s/mm(2). All sequences were repeated with and without repositioning. The peak location, peak height, and mean ADC of the ADC histograms and mean ADC of a region of interest (ROI) in the white matter were compared using paired-sample t tests. Scan-rescan reproducibility was assessed using paired-sample t tests, and repeatability coefficients were reported. With increasing maximum b-values, ADC histograms shifted to lower values, with an increase in peak height ( p<0.01). With FLAIR DWI, the ADC histogram shifted to lower values with a significantly higher, narrower peak ( p<0.01), although the ROI mean ADC showed no significant differences. For scan-rescan reproducibility, no significant differences were observed. Different DWI pulse sequences give rise to different ADC histograms. With a given pulse sequence, however, ADC histogram analysis is a robust and reproducible technique. Using FLAIR DWI, the partial-voluming effect of cerebrospinal fluid, and thus its confounding effect on histogram analyses, can be reduced.

Adult↗

PubMed2003

A framework for a streamline-based probabilistic index of connectivity (PICo) using a structural interpretation of MRI diffusion measurements.

PURPOSE: To establish a general methodology for quantifying streamline-based diffusion fiber tracking methods in terms of probability of connection between points and/or regions. MATERIALS AND METHODS: The commonly used streamline approach is adapted to exploit the uncertainty in the orientation of the principal direction of diffusion defined for each image voxel. Running the streamline process repeatedly using Monte Carlo methods to exploit this inherent uncertainty generates maps of connection probability. Uncertainty is defined by interpreting the shape of the diffusion orientation profile provided by the diffusion tensor in terms of the underlying microstructure. RESULTS: Two candidates for describing the uncertainty in the diffusion tensor are proposed and maps of probability of connection to chosen start points or regions are generated in a number of major tracts. CONCLUSION: The methods presented provide a generic framework for utilizing streamline methods to generate probabilistic maps of connectivity.

Anisotropy↗

PubMed2003

A study of the mechanisms of normal-appearing white matter damage in multiple sclerosis using diffusion tensor imaging--evidence of Wallerian degeneration.

Diffusion tensor imaging (DTI) investigates brain tissue microstructure in vivo. In multiple sclerosis (MS) Wallerian degeneration of axons traversing focal lesions is a potential mechanism of damage in normal-appearing white matter. In vivo evidence for this hypothesis is limited. The present study investigated the relationship between DTI-derived indices in the normal-appearing corpus callosum (CC) and the lesion loads (LLs) in connected cerebral regions. DTI was performed in 39 MS patients and in 21 age-matched controls. Fractional anisotropy (FA) and mean diffusivity (MD) were estimated in the genu, body and splenium of CC. Patients showed lower FA and higher MD in the CC than controls and both correlated with the total LL (r = -0.56 and r = 0.54, p < 0.0001). The LL of individual cerebral lobes correlated with both FA and MD in the corresponding callosal regions, with the body showing the strongest correlations with frontal and parietal LL (p < 0.0001). The strong correlations between DTI indices in the CC and the extent of lesions in connected brain regions support the hypothesis that Wallerian degeneration of axons transected by remote, but connected focal lesions, is an important pathogenic mechanism of damage in MS.

Adult↗

PubMed2003

Combined functional MRI and tractography to demonstrate the connectivity of the human primary motor cortex in vivo.

In this study, we combined advanced MR techniques to explore primary motor cortex (M1) connectivity in the human brain. We matched functional and anatomical information using motor functional MRI (fMRI) and white matter tractography inferred from diffusion tensor imaging (DTI). We performed coregistered DTI and motor task fMRI in 8 right-handed healthy subjects and in 1 right-handed patient presenting with a left precentral tumour. We used the fast-marching tractography (FMT) algorithm to define 3D connectivity maps within the whole brain, from seed points selected in the white matter adjacent to the location of the maximum of fMRI activation. Connectivity maps were then anatomically normalised and analysed using statistical parametric mapping software (SPM99) allowing group comparisons (left versus right hemisphere in control subjects and patient versus control subjects). The results demonstrated, in all control subjects, strong connections from M1 to the pyramidal tracts, premotor areas, parietal cortices, thalamus, and cerebellum. M1 connectivity was asymmetric, being more extensive in the dominant hemisphere. The patient had differences in M1 connectivity from the control group. Thus, fMRI-correlated DTI-FMT is a promising tool to study the structural basis of functional networks in the human brain in vivo.

Adult↗

PubMed2002

Exploring white matter tracts in band heterotopia using diffusion tractography.

Band heterotopia is a malformation of cortical development characterized by bands of gray matter in the white matter parallel to the surface of the neocortex. Histopathological studies have suggested that small white matter tracts pass through the heterotopia, and functional magnetic resonance imaging studies have shown activation in the malformation. We used diffusion tractography to explore the anatomical connectivity of band heterotopia and, in particular, whether in vivo white matter tracts traverse the heterotopic gray matter. Five patients with band heterotopia and five control subjects were scanned with whole brain diffusion tensor imaging. Anisotropy maps were calculated. Using fast marching tractography, we produced maps of connectivity and tract traces from two seed points, in the splenium of the corpus callosum and the right parietal lobe. Eigenvectors were found to pass through the band heterotopia in an aligned fashion. Patterns for maps of connectivity were similar in patients and control subjects. Areas of high connectivity were found in the band heterotopia and in cortical areas on the far side of the malformation from the seed point. The tracts hence appeared to traverse or end within the band heterotopia. The results are in agreement with previous histopathological studies and indicate the structural basis of the functional connectivity and absence of focal deficits in these patients.

Adult↗

PubMed2002

ADC mapping of the human optic nerve: increased resolution, coverage, and reliability with CSF-suppressed ZOOM-EPI.

The mean apparent diffusion coefficient (ADC) of the human optic nerve (ON) has been quantified in vivo, and mean ADC maps are shown along the complete length of the nerve from the globe to the optic chiasm. The mean ADC, over the whole nerve, is shown to be 1058 x 10(-6) mm(2) s(-1) (standard deviation (SD), over nine 3-mm slices, 101x10(-6) mm(2) s(-1); range (833-1178)x10(-6) mm(2) s(-1)). The robustness of the method relies on acquisition of high-resolution coronal images of the ON using the ZOOM-EPI technique, which makes use of a shortened echo train length for increased resolution with decreased susceptibility-induced distortions. Suppression of the cerebrospinal fluid (CSF) and fat signals from tissues that surround the ON also helps successful identification and delineation of the nerve. Averaging of magnitude images is used to compensate for the inherently low signal-to-noise ratio (SNR) of the acquired images; the effects of the Rayleigh distributed noise in such images are allowed for during ADC calculations.

Cerebrospinal Fluid↗

PubMed2002

Initial demonstration of in vivo tracing of axonal projections in the macaque brain and comparison with the human brain using diffusion tensor imaging and fast marching tractography.

Diffusion tensor imaging (DTI), a magnetic resonance imaging technique, is used to infer major axonal projections in the macaque and human brain. This study investigates the feasibility of using known macaque anatomical connectivity as a "gold-standard" for the evaluation of DTI tractography methods. Connectivity information is determined from the DTI data using fast marching tractography (FMT), a novel tract-tracing (tractography) method. We show for the first time that it is possible to determine, in an entirely noninvasive manner, anatomical connection pathways and maps of an anatomical connectivity metric in the macaque brain using a standard clinical scanner and that these pathways are consistent with known anatomy. Analogous human anatomical connectivity is also presented for the first time using the FMT method, and the results are compared. The current limitations of the methodology and possibilities available for further studies are discussed.

Animals↗

PubMed2002

Investigating cervical spinal cord structure using axial diffusion tensor imaging.

This study describes a new technique for Diffusion Tensor Imaging (DTI) that acquires axial (transverse) images of the cervical spinal cord. The DTI images depict axonal fiber orientation, enable quantification of diffusion characteristics along the spinal cord, and have the potential to demonstrate the connectivity of cord white matter tracts. Because of the high sensitivity to motion of diffusion-weighted magnetic resonance imaging and the small size of the spinal cord, a fast imaging method with high in-plane resolution was developed. Images were acquired with a single-shot EPI technique, named ZOOM-EPI (zonally magnified oblique multislice echo planar imaging), which selects localized areas and reduces artefacts caused by susceptibility changes between soft tissue and the adjacent vertebrae. Cardiac gating was used to reduce pulsatile flow artefacts from the surrounding cerebrospinal fluid. Voxel resolution was 1.25 x 1.25 mm(2) in-plane with 5-mm slice thickness. Both the mean diffusivity (MD) and the fractional anisotropy (FA) indices of the cervical spinal cord were measured. The FA index demonstrated high anisotropy of the spinal cord with an average value of 0.61 +/- 0.05 (highest value of 0.66 +/- 0.03 at C3), comparable to white matter tracts in the brain. The diffusivity components parallel and orthogonal to the longitudinal axes of the cord were lambda( parallel) = (1648 +/- 123) x 10(-6) mm(2)s(-1) and lambda( perpendicular) = (570 +/- 47) x 10(-6) mm(2) s(-1), respectively. The high axial resolution allowed preliminary evaluation of fiber connectivity using the fast-marching tractography algorithm, which generated traces of fiber paths consistent with the well-known cord anatomy.

Algorithms↗

PubMed2002

Estimating distributed anatomical connectivity using fast marching methods and diffusion tensor imaging.

A method is presented for determining paths of anatomical connection between regions of the brain using magnetic resonance diffusion tensor information. Level set theory, applied using fast marching methods, is used to generate three-dimensional time of arrival maps, from which connection paths between brain regions may be identified. The method is demonstrated in the normal brain and it is shown that major white matter tracts may be elucidated and that multiple connections and tract branching are allowed. Maps of connectivity between brain regions are also determined. Four options are described for estimating the degree of connectivity between regions.

Algorithms↗