Alonso Pena

Diffusion tensor imaging of brain tumours at 3 T: a potential tool for assessing white matter tract invasion?

AIM To determine whether diffusion tensor imaging (DTI) of brain tumours can demonstrate abnormalities distal to hyperintensities on T2-weighted images, and possibly relate these to tumour grade. MATERIALS AND METHODS Twenty patients with histologically confirmed supratentorial tumours, both gliomas (high and low grade) and metastases, were imaged at 3T using T2-weighted and DTI sequences. Regions of interest (ROI) were drawn within the tumour, in white matter at various distances from the tumour and in areas of abnormality on DTI that appeared normal on T2-weighted images. The relative anisotropy index (RAI)-a measure of white matter organization, was calculated for these ROI. RESULTS The abnormality on DTI was larger than that seen on T2-weighted images in 10/13 patients (77%) with high-grade gliomas. New abnormalities were seen in the contralateral white matter in 4/13 (30%) of these cases. In these high-grade tumours the RAI in areas of white matter disruption with normal appearance on T2-weighted images was reduced (0.19+/-0.04). Even excluding patients with previous radiotherapy this difference remains significant. In all non high-grade tumours (WHO grade II gliomas and metastases) the tumour extent on DTI was identical to the abnormalities shown on T2-weighted imaging and RAI measurements were not reduced (0.3+/-0.04). CONCLUSIONS Subtle white matter disruption can be identified using DTI in patients with high-grade gliomas. Such disruption is not identified in association with metastases or low-grade gliomas despite these tumours producing significant mass effect and oedema. We suggest the changes in DTI may be due to tumour infiltration and that the DTI may provide a useful method of detecting occult white matter invasion by gliomas.

Diffusion tensor imaging in chronic head injury survivors: correlations with learning and memory indices

Diffusion tensor imaging (DTI) provides a unique insight into the cellular integrity of the brain. While conventional magnetic resonance imaging underestimates the extent of pathology following closed head injury, diffusion-weighted imaging has been shown to more accurately delineate the extent of cerebral damage. There have only been a few case studies of DTI in chronic head injury survivors. This study used DTI to investigate changes in anisotropy and diffusivity in survivors of head injury at least 6 months after their injury. The relationship between cognition and diffusion abnormality was also investigated. The voxel-based analysis revealed significant bilateral decreases in anisotropy, in major white matter tracts and association fibers in the temporal, frontal, parietal and occipital lobes. Statistically significant increases in diffusivity were also found in widespread areas of the cortex. A significant positive correlation was found between diffusivity and impairment of learning and memory in the left posterior cingulate, left hippocampal formation and left temporal, frontal and occipital cortex. The common pattern of abnormality despite heterogeneous injury mechanism and lesion location in the group suggests that these cellular changes reflect secondary insults. The importance of diffusion abnormalities in head injury outcome is emphasized by the significant correlation between a learning and memory index and diffusivity in areas known to subserve this cognitive function.

Formal characterization and extension of the linearized diffusion tensor model.

We analyzed the properties of the logarithm of the Rician distribution leading to a full characterization of the probability law of the errors in the linearized diffusion tensor model. An almost complete lack of bias, a simple relation between the variance and the signal‐to‐noise ratio in the original complex data, and a close approximation to normality facilitated estimation of the tensor components by an iterative weighted least squares algorithm. The theory of the linear model has also been used to derive the distribution of mean diffusivity, to develop an informative statistical test for relative lack of fit of the ellipsoidal (or spherical) model compared to an unrestricted linear model in which no specific shape is assumed for the diffusion process, and to estimate the signal‐to‐noise ratios in the original data. The false discovery rate (FDR) has been used to control thresholds for statistical significance in the context of multiple comparisons at voxel level. The methods are illustrated by application to three diffusion tensor imaging (DTI) datasets of clinical interest: a healthy volunteer, a patient with acute brain injury, and a patient with hydrocephalus. Interestingly, some salient features, such as a region normally comprising the basal ganglia and internal capsule, and areas of edema in patients with brain injury and hydrocephalus, had patterns of error largely independent from their mean diffusivities. These observations were made in brain regions with sufficiently large signal‐to‐noise ratios (>2) to justify the assumptions of the log Rician probability model. The combination of diffusivity and its error may provide added value in diagnostic DTI of acute pathologic expansion of the extracellular fluid compartment in brain parenchymal tissue. Hum. Brain Mapping 24:144–155, 2005.

Normal pressure hydrocephalus and cerebral blood flow: a PET study of baseline values

Regional cerebral blood flow (CBF) was studied with O15-water positron emission tomography and anatomic region-of-interest analysis on coregistered magnetic resonance in patients with idiopathic (n = 12) and secondary (n = 5) normal pressure hydrocephalus (NPH). Mean CBF was compared with values obtained from healthy volunteers (n = 12) and with clinical parameters. Mean CBF was significantly decreased in the cerebrum and cerebellum of patients with NPH. The regional analysis demonstrated that CBF was reduced in the basal ganglia and the thalamus but not in white matter regions. The results suggest that the role of the basal ganglia and thalamus in NPH may be more prominent than currently appreciated. The implications for theories regarding the pathogenesis of NPH are discussed.

Effects of brain ventricular shape on periventricular biomechanics: a finite-element analysis.

OBJECTIVE A computer simulation based on the finite-element method was used to study the biomechanics of acute obstructive hydrocephalus and, in particular, to define why periventricular edema is most prominent in the anterior and posterior horns. METHODS Brain parenchyma was modeled as a two-phase material composed of a porous elastic matrix saturated by interstitial fluid. The effects of the cerebrovascular system were not included in this model. The change in the shape of the ventricles as they enlarged was described by two variables, i.e., the stretch of the ependyma and the concavity of the ventricular wall. The distribution of stresses and strains in the tissue was defined by two standard mechanical measures, i.e., the mean effective stress and the void ratio. RESULTS With obstruction to cerebrospinal fluid flow, the simulation revealed that the degree of ventricular expansion at equilibrium depended on the pressure gradient between the ventricles and the subarachnoid space. Periventricular edema was associated with the appearance of expansive (tensile) stresses in the tissues surrounding the frontal and occipital horns. In contrast, the concave shape in the region of the body of the ventricle created compressive stresses in the parenchyma. Both of these stresses seem to be direct consequences of the concave/convex geometry of the ventricular wall, which serves to selectively focus the forces (perpendicular to the ependyma) produced by the increased intraventricular fluid pressure in the periventricular tissues. CONCLUSION The distribution of periventricular edema in acute hydrocephalus is a result not only of increased intraventricular pressure but also of ventricular geometry.

Increased Anisotropy in Acute Stroke A Possible Explanation

Background and Purpose— The increase in fractional anisotropy (FA) in acute stroke has yet to be explained. Using an engineering methodology known as pq diagrams, we sought to explain the increase in FA by describing changes in the total magnitude of the diffusion tensor (L) as well as the isotropic (p) and anisotropic (q) components. Methods— Diffusion tensor imaging was performed in 10 patients with stroke <27 hours old. The diffusion tensor was decomposed into the p and q components and plotted to describe the diffusion trajectories. FA was also calculated and compared. Results— There was significant and consistent reduction in p, q, and L (p: mean, −50.0%; range, −36.6% to −64.5%; q: mean, −50.8%; range, −30.8% to −72.8%; L: mean, −50.3%; range, −37.0% to −65.1%). There were inconsistent changes in FA (mean, −0.5%; range, −44.9% to +45.0%). Five patients had elevated FA due to proportionately higher loss of L than q. Conclusions— Changes in FA only occur when there is a change in the ratio of q/L. Acute elevation of FA occurred in the context of a larger reduction in L than q. The elevation in FA occurs in the context of a reduction in the anisotropic tensor and therefore is a consequence of ratio-metric measurement. This appears to clarify the reported increase in FA in terms of alterations in the shape of the apparent diffusion tensor. pq diagrams appear to offer improved resolution of acute diffusion changes in ischemia.

Changes in Cerebral Blood Flow during Cerebrospinal Fluid Pressure Manipulation in Patients with Normal Pressure Hydrocephalus: A Methodological Study:

The combination of cerebral blood flow measurement using 15O-water positron emission tomography with magnetic resonance coregistration and CSF infusion studies was used to study the global and regional changes in CBF with changes in CSF pressure in 15 patients with normal pressure hydrocephalus. With increases in CSF pressure, there was a variable increase in arterial blood pressure between individuals and global CBF was reduced, including in the cerebellum. Regionally, mean CBF decreased in the thalamus and basal ganglia, as well as in white matter regions. These reductions in CBF were significantly correlated with changes in the CSF pressure and with proximity to the ventricles. A three-dimensional finite-element analysis was used to analyze the effects on ventricular size and the distribution of stress during infusion. To study regional cerebral autoregulation in patients with possible normal pressure hydrocephalus, a sensitive CBF technique is required that provides absolute, not relative normalized, values for regional CBF and an adequate change in cerebral perfusion pressure must be provoked.

Head Circumference and Brain and Hippocampal Volume after Severe Traumatic Brain Injury in Childhood

Vulnerability of the hippocampus to traumatic brain injury (TBI) in adults is related to severity of injury and white matter atrophy. The objectives of this study were to determine features of anthropometry and cerebral morphometry late after TBI in childhood and to assess whether hippocampal volume is related to severity of initial ictus and changes in white matter at follow-up. Thirty-three patients underwent magnetic resonance imaging 4.9 y after severe TBI that necessitated intensive care; 23 had mechanical ventilation and intracranial pressure monitoring longer than 3 d. Magnetic resonance imaging analyses included volume of brain, hemisphere, ventricles, and hippocampal and perihippocampal regions; spatial distribution of voxel-based morphometry differences in white matter; and eigenvalues of diffusion tensor imaging diffusivity. Patients with longer intensive care ictus had smaller-than-expected occipitofrontal head circumference. Eight of these, identified by voxel-based morphometry, had periventricular white matter loss and smaller-than-expected brain volume for OFC, suggesting “atrophy”; the remainder had expected volume for a smaller OFC, suggesting “growth disturbance.” Ninety-three percent of the variation in right hippocampal volume was accounted for by factors related to severity of injury and white matter atrophy. It is concluded that anthropometry and cerebral morphometric measurements late after severe TBI in childhood provides useful outcome data and indicate that, despite adequate growth in stature, effects of TBI on brain growth and hippocampal volume may extend into adulthood.

Communicating Hydrocephalus: The Biomechanics of Progressive Ventricular Enlargement Revisited

BACKGROUND This article investigates the physical mechanisms involved in the chronic ventricular enlargement that accompanies communicating hydrocephalus (CH)--including its normal and low-pressure forms. In particular, it proposes that this phenomenon can be explained by the combined effect of: (a) a reversal of interstitial fluid flow in the parenchyma, and (b) a reduction in the elastic modulus of the cerebral mantle. METHOD To investigate this hypothesis, these changes have been incorporated into a finite element computer simulation of CH, in which brain tissue is idealized as a sponge-like material. The fluid pressure in the lateral ventricles and the subarachnoid space has been set to 10 mmHg, while the fluid pressure inside the parenchyma has been set to 7.5 mmHg. The elastic moduli of white and gray matter have been set to the reduced values of 1 and 5 kPa, respectively. FINDINGS The simulation revealed a substantial ventricular distension (6.5 mm mean outward displacement), which was accompanied by the appearance of stress concentrations in the cerebral mantle. INTERPRETATION These results support the notion that a relative reduction in intraparenchymal fluid pressure coupled with low tissue elasticity can produce both a significant ventricular enlargement and periventricular solid stress concentrations.

Detecting glioma invasion of the corpus callosum using diffusion tensor imaging

We present a patient with a recurrent glioblastoma and abnormalities of the corpus callosum seen on diffusion tensor MRI that were not seen on conventional imaging. These abnormalities preceded the development of the tumour. We describe the technique of diffusion tissue signatures to assess tissue infiltration by tumours compared with values from normal volunteers.