Standard Diffusion Tensor Imaging Research Articles

Motor programme activating therapy influences adaptive brain functions in multiple sclerosis: clinical and MRI study.

There is still little scientific evidence for the efficacy of neurofacilitation approaches and their possible influence on brain plasticity and adaptability. In this study, the outcome of a new kind of neurofacilitation approach, motor programme activating therapy (MPAT), was evaluated on the basis of a set of clinical functions and with MRI. Eighteen patients were examined four times with standardized clinical tests and diffusion tensor imaging to monitor changes without therapy, immediately after therapy and 1 month after therapy. Moreover, the strength of effective connectivity was analysed before and after therapy. Patients underwent a 1-h session of MPAT twice a week for 2 months. The data were analysed by nonparametric tests of association and were subsequently statistically evaluated. The therapy led to significant improvement in clinical functions, significant increment of fractional anisotropy and significant decrement of mean diffusivity, and decrement of effective connectivity at supplementary motor areas was observed immediately after the therapy. Changes in clinical functions and diffusion tensor images persisted 1 month after completing the programme. No statistically significant changes in clinical functions and no differences in MRI-diffusion tensor images were observed without physiotherapy. Positive immediate and long-term effects of MPAT on clinical and brain functions, as well as brain microstructure, were confirmed.

Diffusional kurtosis imaging in hydrocephalus

PurposeDiffusional kurtosis imaging is an advanced diffusion magnetic resonance imaging method that yields, in addition to conventional diffusion information, non-Gaussian diffusion effects, which may allow a more comprehensive characterization of tissue microstructure. The purpose of this study is to use diffusional kurtosis to assess white matter integrity in patients with hydrocephalus and to determine whether changes in kurtosis correlate with the severity of hydrocephalus and leukoaraiosis (LA), a commonly seen comorbidity in hydrocephalus. Methods26 patients with imaging evidence of hydrocephalus and 26 age- and sex- matched subjects with normal ventricular size were retrospectively analyzed. Standard diffusion tensor imaging and diffusional kurtosis metrics were compared between the two groups. Correlation between kurtosis and severity of hydrocephalus and presence and severity of LA was determined. ResultsHydrocephalus patients relative to controls demonstrated statistically significant decrease in all kurtosis metrics in most brain regions studied. The severity of hydrocephalus was associated with greater decrease in kurtosis in the corpus callosum. There was more LA in the hydrocephalus group, and severity of LA was associated with decrease in kurtosis. After controlling for the degree of LA, kurtosis was still decreased in hydrocephalus relative to the controls. ConclusionDiffusional kurtosis imaging detects microstructural changes in the white matter of patients with hydrocephalus. Our results suggest that hydrocephalus plays a role in altering white matter integrity.

White matter microstructure pathology in classic galactosemia revealed by neurite orientation dispersion and density imaging.

White matter abnormalities have been observed in patients with classic galactosemia, an inborn error of galactose metabolism. However, magnetic resonance imaging (MRI) data collected in the past were generally qualitative in nature. Our objective was to investigate white matter microstructure pathology and examine correlations with outcome and behaviour in this disease, by using multi-shell diffusion weighted imaging. In addition to standard diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI) was used to estimate density and orientation dispersion of neurites in a group of eight patients (aged 16–21 years) and eight healthy controls (aged 15–20 years). Extensive white matter abnormalities were found: neurite density index (NDI) was lower in the patient group in bilateral anterior areas, and orientation dispersion index (ODI) was increased mainly in the left hemisphere. These specific regional profiles are in agreement with the cognitive profile observed in galactosemia, showing higher order cognitive impairments, and language and motor impairments, respectively. Less favourable white matter properties correlated positively with age and age at onset of diet, and negatively with behavioural outcome (e.g. visual working memory). To conclude, this study provides evidence of white matter pathology regarding density and dispersion of neurites in these patients. The results are discussed in light of suggested pathophysiological mechanisms.

Regional differences in fiber tractography predict neurodevelopmental outcomes in neonates with infantile Krabbe disease.

BackgroundKrabbe disease is a fatal neurodegenerative disease caused by rapid demyelination of the central and peripheral nervous systems. The only available treatment, unrelated umbilical cord blood transplantation, is effective only if performed before clinical symptoms appear. Phenotypic expressions of disease-causing mutations vary widely, but genotype–phenotype relationships are unclear. Therefore, we evaluated diffusion tensor imaging (DTI) tractography with volumetric analysis as a biomarker of early white matter changes and functional disability in presymptomatic infants.MethodsWe obtained DTI and structural scans of newborns with early-infantile Krabbe disease (n = 9) diagnosed by family history or newborn screening. We compared white matter fiber tract properties to those of normal controls (n = 336) and assessed the ability of tract-based properties to predict longitudinal development in four functional domains (cognitive, fine motor, gross motor, adaptive behavior) after treatment with unrelated umbilical cord blood transplantation. We also assessed the relationship between the standard evaluation (modified Loes score) and DTI results, and the volumetric differences between the Krabbe subjects and normal controls.FindingsReductions in fractional anisotropy were significant in the corticospinal tract in the Krabbe patients compared to controls, which strongly correlated with motor and cognitive outcomes after transplantation. Significant regional differences were observed in the splenium and uncinate fasciculus in Krabbe patients and these differences correlated only with cognitive outcomes. Regional brain volumes of Krabbe patients were slightly larger than controls. Loes scores did not correlate with DTI results.InterpretationNeonatal microstructural abnormalities correlate with neurodevelopmental treatment outcomes in patients treated for infantile Krabbe disease. DTI with quantitative tractography is an excellent biomarker for evaluating infants with Krabbe disease identified through newborn screening.

Quality assurance for diffusion tensor imaging using an ACR phantom: Comparative analysis with 6, 15, and 32 directions at 1.5T and 3.0T MRI systems

Although diffusion tensor imaging (DTI) has been widely used for the quantitative analyses of the integrity of white matter in the brain in clinical and research fields, quality assurance (QA) for DTI has not been fully established. Thus, we suggest a QA guideline for DTI using the American College of Radiology (ACR) Magnetic resonance imaging (MRI) head phantom. In this study, the geometric accuracy, slice-position accuracy, image intensity uniformity, percent signalghosting, low-contrast object detectability, image distortion, fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were measured and evaluated in 1.5T and 3.0T MRI scanners equipped with an 8-channel SENSE head coil. The standard axial spin echo (SE) T1-weighted MR images and DTI with 6, 15 and 32 directions were obtained. Concerning geometric accuracy, image twisting in the three directions was observed due to the inhomogeneity of echo planar imaging (EPI). Image intensity uniformity was significantly lower for DTI than for the standard SE T1-weighted MR images. Percent signal ghosting was higher for images from 3.0T MRI than for images from 1.5T MRI. Low-contrast object detectability was visually identified and measured at a low contrasttonoise ratio (CNR) and a low signaltonoise ratio (SNR). Image distortion changed remarkably to the phaseencoding direction. The present study using the ACR MRI phantom suggests a QA method for DTI with high reproducibility and easy accessibility.

High angular resolution diffusion imaging with stimulated echoes: compensation and correction in experiment design and analysis.

Stimulated echo acquisition mode (STEAM) diffusion MRI can be advantageous over pulsed-gradient spin-echo (PGSE) for diffusion times that are long compared with T2. It therefore has potential for biomedical diffusion imaging applications at 7T and above where T2 is short. However, gradient pulses other than the diffusion gradients in the STEAM sequence contribute much greater diffusion weighting than in PGSE and lead to a disrupted experimental design. Here, we introduce a simple compensation to the STEAM acquisition that avoids the orientational bias and disrupted experiment design that these gradient pulses can otherwise produce. The compensation is simple to implement by adjusting the gradient vectors in the diffusion pulses of the STEAM sequence, so that the net effective gradient vector including contributions from diffusion and other gradient pulses is as the experiment intends. High angular resolution diffusion imaging (HARDI) data were acquired with and without the proposed compensation. The data were processed to derive standard diffusion tensor imaging (DTI) maps, which highlight the need for the compensation. Ignoring the other gradient pulses, a bias in DTI parameters from STEAM acquisition is found, due both to confounds in the analysis and the experiment design. Retrospectively correcting the analysis with a calculation of the full B matrix can partly correct for these confounds, but an acquisition that is compensated as proposed is needed to remove the effect entirely.

Cortico-Cortical, Cortico-Striatal, and Cortico-Thalamic White Matter Fiber Tracts Generated in the Macaque Brain via Dynamic Programming

Probabilistic methods have the potential to generate multiple and complex white matter fiber tracts in diffusion tensor imaging (DTI). Here, a method based on dynamic programming (DP) is introduced to reconstruct fibers pathways whose complex anatomical structures cannot be resolved beyond the resolution of standard DTI data. DP is based on optimizing a sequentially additive cost function derived from a Gaussian diffusion model whose covariance is defined by the diffusion tensor. DP is used to determine the optimal path between initial and terminal nodes by efficiently searching over all paths, connecting the nodes, and choosing the path in which the total probability is maximized. An ex vivo high-resolution scan of a macaque hemi-brain is used to demonstrate the advantages and limitations of DP. DP can generate fiber bundles between distant cortical areas (superior longitudinal fasciculi, arcuate fasciculus, uncinate fasciculus, and fronto-occipital fasciculus), neighboring cortical areas (dorsal and ventral banks of the principal sulcus), as well as cortical projections to the hippocampal formation (cingulum bundle), neostriatum (motor cortical projections to the putamen), thalamus (subcortical bundle), and hippocampal formation projections to the mammillary bodies via the fornix. Validation is established either by comparison with in vivo intracellular transport of horseradish peroxidase in another macaque monkey or by comparison with atlases. DP is able to generate known pathways, including crossing and kissing tracts. Thus, DP has the potential to enhance neuroimaging studies of cortical connectivity.

Loss of Olfactory Tract Integrity Affects Cortical Metabolism in the Brain and Olfactory Regions in Aging and Mild Cognitive Impairment

Olfactory dysfunction is an early feature of Alzheimer disease. This study used multimodal imaging of PET and (18)F-FDG combined with diffusion tensor imaging (DTI) to investigate the association of fiber tract integrity in the olfactory tract with cortical glucose metabolism in subjects with mild cognitive impairment (MCI) and normal controls. We hypothesized that MCI subjects would show loss of olfactory tract integrity and may have altered associations with glucose metabolism. Subjects diagnosed with amnestic MCI (n = 12) and normal controls (n = 23) received standard brain (18)F-FDG PET and DTI with 32 gradient directions on a 3-T MR imaging scanner. Fractional anisotropy (FA) maps were generated. Voxelwise correlation analysis of olfactory tract FA values with (18)F-FDG PET images was performed. Integrated analysis over all subjects indicated a positive correlation between white matter integrity in the olfactory tract and metabolic activity in olfactory processing structures, including the rostral prefrontal cortex, dorsomedial thalamus, hypothalamus, orbitofrontal cortex, and uncus, and in the superior temporal gyrus, insula, and anterior cingulate cortex. Subjects with MCI, compared with normal controls, showed differential associations of olfactory tract integrity with medial temporal lobe and posterior cortical structures. These findings indicate that impairment of axonal integrity or neuronal loss may be linked to functional metabolic changes and that disease-specific neurodegeneration may affect this relationship. Multimodal imaging using (18)F-FDG PET and DTI may provide better insights into aging and neurodegenerative processes.

Fiber type characterization in skeletal muscle by diffusion tensor imaging

Fiber type distribution within a skeletal muscle, i.e. the quantification of the relative amount of type 1 (slow-twitching) and type 2 (fast-twitching) muscle fibers, is of great interest for the monitoring of the effects of training or the treatment of muscle diseases. The purpose of this study was to determine the feasibility of diffusion tensor imaging (DTI) as a tool for noninvasive fiber type quantification in human skeletal muscle. The right calves of 12 healthy volunteers were examined using DTI at 1.5 T. Standard DTI parameters, including fractional anisotropy (FA), and mean, radial and parallel diffusivity (MD, RD and PD, respectively), were determined in the soleus muscle. Fiber type proportion and mean fiber diameter within the soleus muscle were quantified from tissue specimens obtained via a fine needle biopsy. Linear regression analysis tested for associations between DTI and biopsy results. FA values were correlated significantly with fiber type proportion, such that higher FA values indicated a higher proportion of type 1 fibers (R(2) = 0.5, p = 0.01). This was based on lower diffusivity perpendicular to the main axis of the fiber in subjects with a higher type 1 fiber proportion (RD: R(2) = 0.52, p = 0.008). MD was also correlated with the proportion of type 1 fibers (R(2) = 0.37, p = 0.037), whereas PD showed no significant correlation. DTI is a promising method for the noninvasive estimation of fiber type proportion in skeletal muscle. This technique may be used to monitor training effects or may be further developed as a biomarker in certain muscle diseases.

A decision tree for differentiating multiple system atrophy from Parkinson’s disease using 3-T MR imaging

To develop a decision tree based on standard magnetic resonance imaging (MRI) and diffusion tensor imaging to differentiate multiple system atrophy (MSA) from Parkinson's disease (PD). 3-T brain MRI and DTI (diffusion tensor imaging) were performed on 26 PD and 13 MSA patients. Regions of interest (ROIs) were the putamen, substantia nigra, pons, middle cerebellar peduncles (MCP) and cerebellum. Linear, volumetry and DTI (fractional anisotropy and mean diffusivity) were measured. A three-node decision tree was formulated, with design goals being 100 % specificity at node 1, 100 % sensitivity at node 2 and highest combined sensitivity and specificity at node 3. Nine parameters (mean width, fractional anisotropy (FA) and mean diffusivity (MD) of MCP; anteroposterior diameter of pons; cerebellar FA and volume; pons and mean putamen volume; mean FA substantia nigra compacta-rostral) showed statistically significant (P < 0.05) differences between MSA and PD with mean MCP width, anteroposterior diameter of pons and mean FA MCP chosen for the decision tree. Threshold values were 14.6 mm, 21.8 mm and 0.55, respectively. Overall performance of the decision tree was 92 % sensitivity, 96 % specificity, 92 % PPV and 96 % NPV. Twelve out of 13 MSA patients were accurately classified. Formation of the decision tree using these parameters was both descriptive and predictive in differentiating between MSA and PD. • Parkinson's disease and multiple system atrophy can be distinguished on MR imaging. • Combined conventional MRI and diffusion tensor imaging improves the accuracy of diagnosis. • A decision tree is descriptive and predictive in differentiating between clinical entities. • A decision tree can reliably differentiate Parkinson's disease from multiple system atrophy.

Understanding white matter integrity stability for bilinguals on language status and reading performance

Recent studies using diffusion tensor imaging (DTI) have described overall white matter integrity in bilinguals but have not related structural neural pathways to language functions. The current study examined white matter integrity and its relationship to reading skill in monolingual English and bilingual Chinese-English speakers. Eleven monolingual speakers (mean age 28.5 years) and 13 bilingual speakers (mean age 24.2 years; English as a second language was acquired post 5 years of age) participated. Behavioural response times and accuracy rates to name regular and exception words were recorded. Participants were then scanned using a standardized DTI protocol. Fractional anisotropy (FA) and mean diffusivity values were derived from a voxelwise statistical analysis for comparisons between participant groups. Tests for relationships between response time and FA were also conducted. Our results show minimal regions of higher FA for monolinguals when compared to bilinguals and no regions of higher FA for bilinguals when compared to monolinguals, which indicates that white matter integrity may not stabilize in bilinguals until late adulthood. We do show several regions where an increase in FA is associated with faster response times. Interestingly, the FA-response time relationship varies between groups and between word types, which may reflect an increased processing demand for retrieval of difficult words (e.g., exception words). These results provide some support for the interference control and reduced frequency hypotheses outlined by Jones et al. (Cerebr Cortex 22:892-902, 2012). The current findings advance our understanding of the underlying cortical networks associated with language status and reading skill in monolingual and bilingual adults.

Multimodal imaging utilising integrated MR-PET for human brain tumour assessment

The development of integrated magnetic resonance (MR)-positron emission tomography (PET) hybrid imaging opens up new horizons for imaging in neuro-oncology. In cerebral gliomas the definition of tumour extent may be difficult to ascertain using standard MR imaging (MRI) only. The differentiation of post-therapeutic scar tissue, tumour rests and tumour recurrence is challenging. The relationship to structures such as the pyramidal tract to the tumour mass influences the therapeutic neurosurgical approach. The diagnostic information may be enriched by sophisticated MR techniques such as diffusion tensor imaging (DTI), multiple-volume proton MR spectroscopic imaging (MRSI) and functional MRI (fMRI). Metabolic imaging with PET, especially using amino acid tracers such as (18)F-fluoroethyl-L-tyrosine (FET) or (11)C-L-methionine (MET) will indicate tumour extent and response to treatment. The new technologies comprising MR-PET hybrid systems have the advantage of providing comprehensive answers by a one-stop-job of 40-50 min. The combined approach provides data of different modalities using the same iso-centre, resulting in optimal spatial and temporal realignment. All images are acquired exactly under the same physiological conditions. We describe the imaging protocol in detail and provide patient examples for the different imaging modalities such as FET-PET, standard structural imaging (T1-weighted, T2-weighted, T1-weighted contrast agent enhanced), DTI, MRSI and fMRI. Hybrid MR-PET opens up new horizons in neuroimaging. Hybrid MR-PET allows brain tumour assessment in one stop. Hybrid MR-PET allows simultaneous acquisition of structural, functional and molecular images.

Visualization of resting‐state networks in utero

Functional magnetic resonance imaging (fMRI) allowsthe visualization of brain function and processing ofversatile inputs of the human brain. Recently, thismethod has been shown to provide insights into thespatiotemporal distribution of processing networks thatcan be demonstrated to be active in the brain even inthe absence of a task when the brain is ‘at rest’. Theseso-called resting-state networks (RSNs), characterizedby spontaneous intrinsic fluctuations between 0.01 and0.1 Hz, have been repeatedly and reproducibly found tobe organized into specific functional networks across thebrain

Continuing the search for MR imaging biomarkers for MGMT promoter methylation status: conventional and perfusion MRI revisited

Continuing the search for MR imaging biomarkers for MGMT promoter methylation status: conventional and perfusion MRI revisited

Diffusion kurtosis as an in vivo imaging marker for reactive astrogliosis in traumatic brain injury.

Diffusion Kurtosis Imaging (DKI) provides quantifiable information on the non-Gaussian behavior of water diffusion in biological tissue. Changes in water diffusion tensor imaging (DTI) parameters and DKI parameters in several white and gray matter regions were investigated in a mild controlled cortical impact (CCI) injury rat model at both the acute (2 h) and the sub-acute (7 days) stages following injury. Mixed model ANOVA analysis revealed significant changes in temporal patterns of both DTI and DKI parameters in the cortex, hippocampus, external capsule and corpus callosum. Post-hoc tests indicated acute changes in mean diffusivity (MD) in the bilateral cortex and hippocampus (p<0.0005) and fractional anisotropy (FA) in ipsilateral cortex (p<0.0005), hippocampus (p=0.014), corpus callosum (p=0.031) and contralateral external capsule (p=0.011). These changes returned to baseline by the sub-acute stage. However, mean kurtosis (MK) was significantly elevated at the sub-acute stages in all ipsilateral regions and scaled inversely with the distance from the impacted site (cortex and corpus callosum: p<0.0005; external capsule: p=0.003; hippocampus: p=0.011). Further, at the sub-acute stage increased MK was also observed in the contralateral regions compared to baseline (cortex: p=0.032; hippocampus: p=0.039) while no change was observed with MD and FA. An increase in mean kurtosis was associated with increased reactive astrogliosis from immunohistochemistry analysis. Our results suggest that DKI is sensitive to microstructural changes associated with reactive astrogliosis which may be missed by standard DTI parameters alone. Monitoring changes in MK allows the investigation of molecular and morphological changes in vivo due to reactive astrogliosis and may complement information available from standard DTI parameters. To date the use of diffusion tensor imaging has been limited to study changes in white matter integrity following traumatic insults. Given the sensitivity of DKI to detect microstructural changes even in the gray matter in vivo, allows the extension of the technique to understand patho-morphological changes in the whole brain following a traumatic insult.

Renal diffusion tensor imaging: is it possible to define the tubular pathway? A case report

The authors report a case of unilateral xanthogranulomatous pyelonephritis, associated with chronic lithiasis studied by standard clinical magnetic resonance imaging protocol and diffusion tensor imaging (DTI). Maps of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) and tractography were reconstructed on both healthy and pathologic kidney. ADC and FA values are in agreement with the literature. Tractography reconstruction of tubular renal architecture was confirmed by histology. This result suggests the potential ability of DTI to detect structural alterations in the architecture of the kidney, as noninvasive tool, preceding the onset of clinical-laboratory alterations.

Cerebral Network Disruption as a Possible Mechanism for Impaired Recovery after Acute Pontine Stroke

Background: Recovery from stroke is presumed to be a function of a widespread cerebral network. Chronic white matter lesions (WML) have been proposed to be a predictor of poor outcome after acute stroke. We tested the hypothesis that the extent of WML has an effect on functional recovery in acute pontine stroke by disrupting the integrity of the supratentorial cerebral network. Methods: Seventeen patients with acute unilateral pontine stroke who had received a standardized stroke workup and additional diffusion tensor imaging (DTI) were studied. After grading the extent of WML according to the Fazekas scale and semiautomated lesion volume calculation, we compared patients with acute pontine infarction and advanced WML to those with absent or minimal WML regarding baseline characteristics, stroke subtype and clinical outcome. In addition, we used tract-based spatial statistics for voxel-wise analysis of the DTI-derived parameter fractional anisotropy in the white matter tracts. Results: The volume of WML ranged between 0.1 and 42.1 cm³ (mean = 15.9) and was graded as follows: 0 in 5.9%, 1 in 35.3%, 2 in 41.2% and 3 in 17.6%. Both patients with Fazekas grades 2–3 (p = 0.014) as well as those with larger WML volumes (p = 0.037) had severer functional deficits at the 3-month follow-up. White matter tracts displaying a significant decrease in fractional anisotropy values were the corpus callosum, the anterior thalamic radiation and the inferior fronto-occipital fasciculus. Conclusions: Chronic WML contribute to a less favorable clinical outcome after pontine stroke depending on (1) the extent of pre-existing WML and (2) the degree of disruption of cerebral connectivity as indicated by reduced tissue integrity in the white matter not affected by WML as detected by DTI and tract-based spatial statistics.

Changes in extratemporal integrity and cognition in temporal lobe epilepsy: A diffusion tensor imaging study

Diffusion tensor imaging (DTI) is a sensitive technique for studying cerebral white matter. Only a few studies have examined the association between changes in extratemporal integrity and cognition in temporal lobe epilepsy (TLE), especially in Chinese patients. We used DTI to characterize microstructural changes and investigate their associations with cognition in patients with temporal lobe epilepsy. We studied 27 adult patients with TLE and 21 healthy controls. A standardized neuropsychological evaluation and diffusion tensor imaging examination were conducted on each subject. Eight patients were excluded because T2-weighted magnetic resonance imaging (MRI) results showed visible lesions. Furthermore, we determined mean diffusivity (MD) and fractional anisotropy (FA) values in the different regions of interest - normal-appearing white matter (NAWM) in the frontal lobe white matter, the occipital lobe white matter, the corpus callosum, the internal capsules, the external capsules; and normal-appearing gray matter (NAGM) in the caudate nucleus head, the putamens and the thalami. These diffusion measurements were compared between the two groups, and we examined the correlations between DTI values and clinical characteristics. In addition, multiple linear regression analysis was used to study the association of DTI values with cognitive function. Compared with normal controls, TLE patients demonstrated decreased FA in NAGM of both thalami and NAWM of the posterior limb of the left internal capsule (P<.01). In patients with temporal lobe epilepsy, right thalamus FA showed a tendency to correlate with age at seizure onset (ß=0.47, P=.045), and left thalamus MD showed a tendency to correlate with the duration of epilepsy (ß=0.54 P=.038). Patients with temporal lobe epilepsy showed significantly poorer performance on nearly all tasks concerning category fluency and other executive functions (P<.01). In patients with TLE, there was a positive correlation between category fluency scores and FA in the white matter of the left frontal lobe (ß=0.429, P=.041) and the right occipital lobe (ß=0.613, P=.001). Our results suggested that the thalamus might be a potentially important extratemporal structure involved in temporal lobe epilepsy. Moreover, a longer duration of epilepsy or an earlier age at onset may result in more abnormalities in the thalamus. Patients with temporal lobe epilepsy showed significantly poorer performance on nearly all tasks concerning category fluency and other executive functions. Our results showed that frontal lobe white matter contributed to category fluency impairment in patients with TLE, but other areas might also contribute to these impairments.

Combinatorial fiber-tracking of the human brain

This paper presents a novel fiber-tracking algorithm, termed combinatorial tracking, which uses stochastic process modeling and global optimization algorithm for tractography. Combinatorial tracking is a probabilistic tracking algorithm that transforms the brain's white matter into a grid in which each voxel has 26 weighted connections with adjacent voxels. We model the random walk on this graph using a Markov Chain model and suggest two approaches for fiber reconstruction. In the first approach, we find the most probable paths between two voxels with prior connectivity knowledge using a shortest path algorithm. In the second approach, the all-pairs mean first passage time (MFPT) matrix M (or hitting time as referred to in the Spectral Graph theory literature) is calculated analytically. We suggest that M can be interpreted as a global connectivity matrix and use it for fiber reconstruction. We also introduce a simulation framework that can be used to calculate specific elements of the matrix M, and show how it can be employed to select the target of a fiber in a high resolution diffusion tensor imaging (DTI) dataset. Because any source and any target voxel can be connected, combinatorial tracking permits true connectivity analysis, overcoming the limitations of conventional tracking, especially stopping criteria (e.g. low FA). We applied combinatorial tracking to a standard DTI dataset and demonstrated the reconstruction of the cortico-thalamic pathway, the pyramidal decussation, and the medial cerebellar peduncle fibers. While the DTI ellipsoid served as input for the algorithms, any diffusion imaging based orientation density function (ODF) can be used. This framework can potentially turn diffusion imaging tractography into a true connectivity measure.

MRI Detection of the Cerebellar Syndrome in Creutzfeldt–Jakob Disease

Creutzfeldt-Jakob Disease (CJD) is characterized by bilateral basal ganglia hyperintensities on T2W and diffusion-weighted imaging (DWI) magnetic resonance imaging (MRI) scans, consistent with its extrapyramidal neurological manifestations. MRI is diagnostically uninformative about the cerebellar symptoms, equally prominent in CJD. This study was undertaken to explain this apparent paradox. Eleven CJD patients with definite cerebellar or brain stem symptoms were selected from a large prospective study, as well as 11 healthy controls matched for age and gender. All subjects participated in a standardized MRI protocol, including SPGR, fluid-attenuated inversion recovery (FLAIR), DWI and diffusion tensor imaging (DTI). All subjects underwent detailed examination by a neurologist blinded to the radiological findings, who predicted the expected site of cerebral abnormalities. MRI showed good sensitivity for the abnormalities predicted in the cortex (80-90%) and basal ganglia (100%). None of the standard MRI sequences, including DWI, DTI, and FLAIR, revealed any tissue abnormalities in cerebellum or brain stem. Apparent diffusion coefficient (ADC) values, however, were substantially and significantly elevated in several cerebellar structures, where also the volumetric (VBM) analysis revealed elevated cerebrospinal fluid volume, suggesting focal cerebellar atrophy in these CJD patients. In patients with CJD, DWI appears sensitive to the reduced diffusivity in cortex and basal ganglia but insensitive to cerebellar involvement. We propose that the radiological hallmark of cerebellar pathology in CJD is atrophy, revealed quantitatively by both VBM and elevated diffusivity, which is identifiable on ADC maps but poorly visualized in nonquantitative DWI images.