Color schemes to represent the orientation of anisotropic tissues from diffusion tensor data: application to white matter fiber tract mapping in the human brain
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Journal Article↗
Biomedical subjects
C Pierpaoli
Publications and source records attributed to C Pierpaoli.
In vivo fiber tractography using DT-MRI data.
Fiber tract trajectories in coherently organized brain white matter pathways were computed from in vivo diffusion tensor magnetic resonance imaging (DT-MRI) data. First, a continuous diffusion tensor field is constructed from this discrete, noisy, measured DT-MRI data. Then a Frenet equation, describing the evolution of a fiber tract, was solved. This approach was validated using synthesized, noisy DT-MRI data. Corpus callosum and pyramidal tract trajectories were constructed and found to be consistent with known anatomy. The method's reliability, however, degrades where the distribution of fiber tract directions is nonuniform. Moreover, background noise in diffusion-weighted MRIs can cause a computed trajectory to hop from tract to tract. Still, this method can provide quantitative information with which to visualize and study connectivity and continuity of neural pathways in the central and peripheral nervous systems in vivo, and holds promise for elucidating architectural features in other fibrous tissues and ordered media.
Artifacts↗
Visualizing and characterizing white matter fiber structure and architecture in the human pyramidal tract using diffusion tensor MRI.
We used diffusion tensor imaging to assess diffusion anisotropy in the pyramidal tract in ten young, and ten elderly subjects (five males and five females in each group). The purpose of this study was to define normative values for anisotropy at different anatomic levels of the brainstem as well as to assess differences due to age, gender, and laterality. In all subjects, anisotropy was highest in the cerebral peduncle, lowest in the caudal pons, and intermediate in the medulla. In the pons and medulla the regional variability was high, with significant differences in anisotropy even between contiguous slices. Multifactorial ANOVA (performed using the average value of anisotropy within each region of interest) revealed that elderly subjects had significantly lower values than young subjects in the cerebral peduncle, with no differences in the pons and medulla. No significant differences in anisotropy due to gender and side were found. The differences in anisotropy at different levels of the brainstem reflect differences in the local architecture of white matter fibers. Anisotropy is high in the cerebral peduncle because fibers have a highly ordered arrangement, while in the pons and medulla, anisotropy is lower because the local fiber architecture is less coherent due to the presence of other fibers and nuclei. The biologic meaning of the intergroup differences in anisotropy is discussed in light of the structure and architecture of the tissue under investigation. We also consider potential sources of artifacts, such as noise and motion, partial volume contamination, anatomic mismatching, and the use of inappropriate statistical tests. We conclude that the age-related decrease in anisotropy in the cerebral peduncle is not artifactual but rather reflects subtle structural changes of the aging white matter. Our study however shows that caution must be exercised in interpreting diffusion anisotropy data.
Adult↗
Comparative MR imaging study of brain maturation in kittens with T1, T2, and the trace of the diffusion tensor.
PURPOSE: To assess the time-course of the relaxation times and the orientationally averaged water diffusion coefficient Doav in postnatal brain development. MATERIALS AND METHODS: Multisection maps of T1, T2, and the trace of the diffusion tensor (Trace[D] = 3 x Doav) were obtained in four kittens at eight time points. RESULTS: In the adult, Doav was about 700 micron 2/sec in both white and gray matter. In the newborn, Doav was 1,100-1,350 micron 2/sec in white matter and 1,000 micron 2/sec in gray matter. For all anatomic regions and time points, the correlation between Doav and 1/T2 was high (R2 = 0.87, P << .001). T1 showed a lower correlation with Doav and a higher sensitivity to myelinization than did T2. CONCLUSION: Although Doav shows dramatic changes in the maturing brain, the high correlation between Doav and T2 indicates that little additional information can be obtained by measuring this diffusion parameter during normal brain development. This contrasts with previous findings in brain ischemia, where Doav and T2 appear to be uncorrelated. After including the authors' data and published iontophoretic measurements in a simple model of diffusion in tissues, the authors suggest that the underlying mechanisms of Doav reduction in brain maturation and ischemia are different. Doav changes during development are mainly affected by events occurring in the cellular compartment, while changes in extracellular volume fraction and tortuosity, which are thought to determine the reduction in Doav during ischemia, are probably of secondary importance.
Animals↗
Color schemes to represent the orientation of anisotropic tissues from diffusion tensor data: application to white matter fiber tract mapping in the human brain.
This paper investigates the use of color to represent the directional information contained in the diffusion tensor. Ideally, one wants to take into account both the properties of human color vision and of the given display hardware to produce a representation in which differences in the orientation of anisotropic structures are proportional to the perceived differences in color. It is argued here that such a goal cannot be achieved in general and therefore, empirical or heuristic schemes, which avoid some of the common artifacts of previously proposed approaches, are implemented. Directionally encoded color (DEC) maps of the human brain obtained using these schemes clearly show the main association, projection, and commissural white matter pathways. In the brainstem, motor and sensory pathways are easily identified and can be differentiated from the transverse pontine fibers and the cerebellar peduncles. DEC maps obtained from diffusion tensor imaging data provide a simple and effective way to visualize fiber direction, useful for investigating the structural anatomy of different organs. Magn Reson Med 42:526-540, 1999.
Anisotropy↗
Characterization of and correction for eddy current artifacts in echo planar diffusion imaging.
Magnetic resonance diffusion imaging is potentially an important tool for the noninvasive characterization of normal and pathological tissue. The technique, however, is prone to a number of artifacts that can severely affect its ability to provide clinically useful information. In this study, the problem of eddy current-induced geometric distortions that occur in diffusion images acquired with echo planar sequences was addressed. These geometric distortions produce artifacts in computed maps of diffusion parameters and are caused by misalignments in the individual diffusion-weighted images that comprise the diffusion data set. A new approach is presented to characterize and calibrate the eddy current effects, enabling the eddy current distortions to be corrected in sets of interleaved (or snapshot) echo planar diffusion images. Correction is achieved by acquiring one-dimensional field maps in the read and phase encode direction for each slice and each diffusion step. The method is then demonstrated through the correction of distortions in diffusion images of the human brain. It is shown that by using the eddy current correction scheme outlined, the eddy current-induced artifacts in the diffusion-weighted images are almost completely eliminated. In addition, there is a significant improvement in the quality of the resulting diffusion tensor maps.
Artifacts↗
A simplified method to measure the diffusion tensor from seven MR images.
Analytical expressions of the diffusion tensor of water, D, and of scalar invariants derived from it, are given in terms of the intensities of seven diffusion-weighted images (DWIs). These formulas simplify the post-processing steps required in diffusion tensor imaging, including estimating D in each voxel (from the set of b-matrices and their corresponding DWIs), and then computing its eigenvalues, eigenvectors, and scalar invariants. In a study conducted using artifact-free DWIs with high diffusion weighting (bmax approximately 900 s/mm2, maps of Trace(D) and the Relative and Lattice Anisotropy indices calculated analytically and by multivariate linear regression showed excellent agreement in brain parenchyma of a healthy living cat. However, the quality of the analytically computed maps degraded markedly as diffusion weighting was reduced. Although diffusion tensor MRI with seven DWIs may be useful for clinical applications where rapid scanning and data processing are required, it does not provide estimates of the uncertainty of the measured imaging parameters, rendering it susceptible to noise and systematic artifacts. Therefore, care should be taken when using this technique in radiological applications.
Animals↗
Simultaneous measurement of DeltaR2 and DeltaR2* in cat brain during hypoxia and hypercapnia.
One of the most important issues in blood-oxygen-level-dependent (BOLD)-based brain functional magnetic resonance imaging is the understanding of the vascular structures that are responsible for the signal changes observed. The T2*-related signal changes observed during variations in susceptibility-induced magnetic field gradients are a function both of non-refocusable mechanisms, such as diffusion, and of refocusable effects such as field inhomogeneities. Conversely, T2-related signal changes are only a function of non-refocusable effects. It has been suggested that T2-weighted images could be less sensitive to blood susceptibility changes in a macrovascular environment than T2*-weighted images and could thus be more accurate in identifying the "activation" of the parenchyma rather than "draining vein" effects. In this study we use hypoxia and hypercapnia challenges in cats to provide a change in blood deoxyhemoglobin concentration (as a model for classic BOLD changes and not as a model for neuronal activation). A combined gradient echo and spin echo echo-planar-imaging (EPI) pulse sequence was used to map DeltaR2 (i.e., Delta(1/T2)) and DeltaR2* (i.e., Delta(1/T2*)) changes during the challenges. Our experiments demonstrate that: (i) the acquisition of T2-weighted EPI data does not in itself differentiate signal changes in the parenchyma from those occurring in regions around larger vessels, but that (ii) the simultaneous acquisition of T2- and T2*-weighted images could be useful in identifying microvascular regions in gray matter by analyzing the ratio DeltaR2/DeltaR2*. This value seems independent of the degree of deoxyhemoglobin concentration change, but is related to properties of the vascular environment. We suggest a possible application of the results to the study of brain function in humans.
Animals↗
Toward a quantitative assessment of diffusion anisotropy.
Indices of diffusion anisotropy calculated from diffusion coefficients acquired in two or three perpendicular directions are rotationally variant. In living monkey brain, these indices severely underestimate the degree of diffusion anisotropy. New indices calculated from the entire diffusion tensor are rotationally invariant (RI). They show that anisotropy is highly variable in different white matter regions depending on the degree of coherence of fiber tract directions. In structures with a regular, parallel fiber arrangement, water diffusivity in the direction parallel to the fibers (Dparallel approximately 1400-1800 x 10(-6) mm2/s) is almost 10 times higher than the average diffusivity in directions perpendicular to them (D + D)/2 [corrected] approximately 150-300 x 10(-6) mm2/s), and is almost three times higher than previously reported. In structures where the fiber pattern is less coherent (e.g., where fiber bundles merge), diffusion anisotropy is significantly reduced. However, RI anisotropy indices are still susceptible to noise contamination. Monte Carlo simulations show that these indices are statistically biased, particularly those requiring sorting of the eigenvalues of the diffusion tensor based on their magnitude. A new intervoxel anisotropy index is proposed that locally averages inner products between diffusion tensors in neighboring voxels. This "lattice" RI index has an acceptably low error variance and is less susceptible to bias than any other RI anisotropy index proposed to date.
Animals↗
Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI.
Quantitative-diffusion-tensor MRI consists of deriving and displaying parameters that resemble histological or physiological stains, i.e., that characterize intrinsic features of tissue microstructure and microdynamics. Specifically, these parameters are objective, and insensitive to the choice of laboratory coordinate system. Here, these two properties are used to derive intravoxel measures of diffusion isotropy and the degree of diffusion anisotropy, as well as intervoxel measures of structural similarity, and fiber-tract organization from the effective diffusion tensor, D, which is estimated in each voxel. First, D is decomposed into its isotropic and anisotropic parts, [D] I and D - [D] I, respectively (where [D] = Trace(D)/3 is the mean diffusivity, and I is the identity tensor). Then, the tensor (dot) product operator is used to generate a family of new rotationally and translationally invariant quantities. Finally, maps of these quantitative parameters are produced from high-resolution diffusion tensor images (in which D is estimated in each voxel from a series of 2D-FT spin-echo diffusion-weighted images) in living cat brain. Due to the high inherent sensitivity of these parameters to changes in tissue architecture (i.e., macromolecular, cellular, tissue, and organ structure) and in its physiologic state, their potential applications include monitoring structural changes in development, aging, and disease.
Animals↗
High temporal resolution diffusion MRI of global cerebral ischemia and reperfusion.
Although brain ischemia has been extensively studied using diffusion-weighted magnetic resonance imaging, most studies performed so far have not had adequate time resolution to follow the temporal changes in the water apparent diffusion coefficient (ADC) in hyperacute ischemia. Using diffusion echo planar imaging, we obtained ADC maps (calculated from measurements made with 8 b-values) with a time resolution of 43 s in a feline model of global brain ischemia and reperfusion. Different protocols were performed: 10-min hypoperfusion, 10- and 22-min ischemia followed by reperfusion, and cardiac arrest. ADC values were obtained from white matter of the internal capsule and from the thalamus. Cortical gray matter measurements were not deemed reliable due to the close proximity of CSF in the cortical sulci. Following occlusion, the ADC declined in the thalamus to < 2 SD of its normal baseline value within 1.5-2.5 min. This decay was exponential with a time constant (tau +/- SD) of 6.0 +/- 2.6 min; no further decrease in the ADC was observed 10 min following ischemia. Following reperfusion, in animals that showed ADC recovery, the ADC began increasing immediately, returning to its preischemic value in approximately 15 min. No significant ADC changes were observed during hypoperfusion. Following cardiac arrest, the decay of ADC was more rapid in the thalamus (tau = 2.6 +/- 0.6 min) than in white matter (tau = 6.6 +/- 1.8 min). We observed that the ADC at 40 min after cardiac arrest was similar to the ADC at 10 min after ischemia. Given that all animals subjected to 10-min ischemic episodes showed ADC recovery with reperfusion, doubt is cast on whether it is possible to define a threshold value of the ADC below which brain tissue is irreversibly damaged. Finally, despite variability in the time constants of the ADC decay induced by ischemia, the ADC values at 10 min were very similar in all the animals. This suggests that when blood flow is diminished sufficiently to induce an ADC reduction, differences in perfusion affect the rapidity of the decrease but not the final asymptotic value reached.
Animals↗
Diffusion tensor MR imaging of the human brain.
PURPOSE: To assess intrinsic properties of water diffusion in normal human brain by using quantitative parameters derived from the diffusion tensor, D, which are insensitive to patient orientation. MATERIALS AND METHODS: Maps of the principal diffusivities of D, of Trace(D), and of diffusion anisotropy indices were calculated in eight healthy adults from 31 multisection, interleaved echo-planar diffusion-weighted images acquired in about 25 minutes. RESULTS: No statistically significant differences in Trace(D) (approximately 2,100 x 10(-6) mm2/sec) were found within normal brain parenchyma, except in the cortex, where Trace(D) was higher. Diffusion anisotropy varied widely among different white matter regions, reflecting differences in fiber-tract architecture. In the corpus callosum and pyramidal tracts, the ratio of parallel to perpendicular diffusivities was approximately threefold higher than previously reported, and diffusion appeared cylindrically symmetric. However, in other white matter regions, particularly in the centrum semiovale, diffusion anisotropy was low, and cylindrical symmetry was not observed. Maps of parameters derived from D were also used to segment tissues based on their diffusion properties. CONCLUSION: A quantitative characterization of water diffusion in anisotropic, heterogeneously oriented tissues is clinically feasible. This should improve the neuroradiologic assessment of a variety of gray and white matter disorders.
Adult↗
Effect of anticonvulsant drugs on peripheral benzodiazepine receptors of human lymphocytes.
Anticonvulsant drugs, such as carbamazepine, may exert some of their effects through peripheral benzodiazepine receptors (PBR), which are present in glial cells and regulate the synthesis of neurosteroids. PBR have also been demonstrated in human lymphocytes, where they might be used as peripheral markers of anticonvulsant drug effects. In the present paper we investigated the interaction of various antiepileptic drugs with PBR of human lymphocytes and evaluated possible effects of acute and chronic treatment with these drugs. At normal therapeutic concentrations, diazepam, carbamazepine and phenobarbital occupy respectively 70, 30 and 10% of PBR sites in human lymphocytes. Although no change of receptor density or affinity was observed after acute in vitro treatment, in epileptic patients chronically treated with carbamazepine, phenobarbital and valproic acid, PBR Bmax was increased with respect to controls and untreated epileptics. Since PBR of human lymphocytes may be affected by anticonvulsant drug treatment, we suggest that they might be involved in the immunological alterations reported in these patients and might be used as peripheral markers of drug effects on the central nervous system.
Adolescent↗
Blue blood or black blood: R1 effects in gradient-echo echo-planar functional neuroimaging.
Changes in the longitudinal relaxation rate (R1) may play a role in the MRI signal intensity increases that have been associated with physiological brain activation. We used gradient-echo echo-planar MRI (GRE-EPI) to test whether physiological activations associated with hypercapnia in dogs were dependent on the delay (TR) between successive images in a time-series. Our results show that, in addition to activation-induced changes in the R2 (transverse relaxation including inhomogeneity effects), activation-induced changes in R1 are significant under certain pulsing conditions. In our paradigm, the R1 contribution became significant at TR values of 1 s or less.
Animals↗
Peripheral benzodiazepine receptors and glucose metabolism in human gliomas.
Peripheral benzodiazepine receptors (PBR) are increased in gliomas and augmented glucose metabolism is seen in malignant brain tumors. We investigated the relationship between PBR density (Bmax) and glucose utilization rate (GUR) in 17 patients with cerebral gliomas of different grades. PBR Bmax was assessed by [3H]PK-11195 in vitro binding in surgical specimens and GUR was measured by Positron Emission Tomography with [18F]2-Fluorodeoxyglucose before the surgery. In untreated tumors there was a positive correlation between PBR Bmax and GUR (2r = 0.84). This correlation was not observed in patients who had been treated with radiation and/or chemotherapy prior to surgery (r2 = 0.13). In addition, in untreated patients, the increase in PBR density and GUR appeared to be related to the degree of malignancy.
Adult↗
Brain parenchyma apparent diffusion coefficient alterations associated with experimental complex partial status epilepticus.
The objective of this study was to evaluate whether water apparent diffusion coefficient (ADC) measurements provide more specific information than T2-weighted MRI about the evolution of brain parenchyma lesions secondary to prolonged complex partial seizures. We measured the ADC in the brain of rats exhibiting prolonged complex partial seizures induced by intraperitoneal injection of kainic acid (KA). The animals were imaged with diffusion and T2-weighted MRI at 2 T from 3 h up to 9 days after KA injection. In the piriform cortex and amygdala, the T2-weighted MRI signal intensity appeared to be uniformly increased from 24 to 72 h after KA injection, and returned to normal by 9 days. In the same regions between 24 and 72 h, the ADC first decreased and then increased. The ADC changes were consistent with the known histopathologic alterations. In this complex partial seizure model, the ADC measurement provides more specific information than T2-weighted MRI about the histopathologic evolution of the lesions. This supports the proposal that diffusion MRI may be valuable for the evaluation of the neuropathologic sequelae in patients with multiple or prolonged seizures.
Animals↗
Benzodiazepine receptors and diazepam binding inhibitor: a possible link between stress, anxiety and the immune system.
This review summarizes the evidence available on the involvement in stress of different classes of benzodiazepine receptors and their putative endogenous ligand, diazepam binding inhibitor (DBI), with particular reference to their role in modifications of the immune response. The presented data from in vitro, experimental, and clinical studies suggest that benzodiazepine receptors and DBI play a major role in regulating steroid production in both the adrenals and central nervous system, and may be involved in the activation of the hypothalamic-pituitary-adrenal axis in stress response.
Animals↗
Histopathologic correlates of abnormal water diffusion in cerebral ischemia: diffusion-weighted MR imaging and light and electron microscopic study.
PURPOSE: To correlate the findings on diffusion-weighted magnetic resonance (MR) images with the cytologic and histologic findings in ischemic tissue. MATERIALS AND METHODS: A photochemical model of cerebral infarction in rats was studied with diffusion- and T2-weighted MR imaging. The development of lesions was followed from 20 minutes to 5 days after the onset of ischemia. Apparent water diffusion coefficient (ADC) maps were calculated and correlated with light and electron microscopic findings. RESULTS: T2-weighted images clearly showed vasogenic edema but did not enable distinction between areas with cellular damage and the surrounding edematous regions. In contrast, the ADC, which was elevated in nonischemic edematous regions, was diminished in areas with histologic evidence of ischemic damage or necrosis. In the core of the infarct, the ADC became elevated when electron microscopy revealed cellular lysis. CONCLUSION: Diffusion-weighted images may help ascertain the extent of cellular damage and death after stroke.
Animals↗