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PubMed2004

Diffusion magnetic resonance imaging patterns in metabolic and toxic brain disorders.

PURPOSE: To evaluate metabolic and toxic brain disorders that manifest with restricted, elevated, or both restricted and elevated diffusion patterns on diffusion magnetic resonance imaging (MRI). MATERIAL AND METHODS: Echo-planar diffusion MRI examinations were obtained in 34 pediatric patients with metabolic and toxic brain disorders proved by appropriate laboratory studies. The MRI unit operated at 1.5 T with a gradient strength of 30 mT/ meter, and a rise time of 600 micros. b=1000s/mm2 images and apparent diffusion coefficient (ADC) maps with ADC values were studied. RESULTS: Three patterns were observed: 1. A restricted diffusion pattern (high signal on b = 1000 s/mm2 images and low ADC values); 2. an elevated diffusion pattern (normal signal on b = 1000s/mm2 images and high ADC values); and 3. a mixed pattern (coexistent restricted and increased diffusion patterns in the same patient). Disorders manifesting with a restricted diffusion pattern included metachromatic leukodystrophy (n = 2), phenylketonuria (n = 3), maple syrup urine disease (intermediate form) (n = 1), infantile neuroaxonal dystrophy (n = 1), Leigh (n = 2), Wilson (n = 3), and Canavan disease (n = 1). Disorders with an elevated diffusion pattern included phenylketonuria (n = 1), adrenoleukodystrophy (n = 1), merosin-deficient congenital muscular dystrophy (n = 2), mucopolysaccharidosis (n = 2), Lowe syndrome (n = 1), Leigh (n = 2), Alexander (n = 1), Pelizaeus-Merzbacher (n = 1), and Wilson (n = 3) disease. Disorders with a mixed pattern included L-2 hydroxyglutaric aciduria (n = 2), non-ketotic hyperglycinemia (n = 1), infantile neuroaxonal dystrophy (n =2), maple syrup urine disease (n = 1), and Leigh (n = 1) disease. CONCLUSION: The findings suggested that the three different diffusion patterns reflect the histopathological changes associated with the disorders and different stages of a particular disorder. It is likely that the restricted diffusion pattern corresponds to abnormalities related to myelin, and the elevated diffusion pattern to disintegration of the tissue. The mixed pattern has contributions from both myelin abnormalities related to myelin disintegration of the tissue.

Adolescent↗

PubMed1982

Diffusion of low density lipoprotein-receptor complex on human fibroblasts.

Diffusion of the complex consisting of low density lipoprotein (LDL) bound to its receptor on the surface of human fibroblasts has been measured with the help of an intensely fluorescent, biologically active LDL derivative, dioctadecylindocarbocyanine LDL (dil(3)-LDL). Fluorescence photobleaching recovering and direct video observations of the Brownian motion of individual LDL-receptor complexes yielded diffusion coefficients for the slow diffusion on cell surfaces and fast diffusion on membrane blebs, respectively. At 10 degrees C, less that 20 percent of the LDL-receptor complex was measurably diffusible either on normal human fibroblasts GM-3348 or on LDL-receptor- internalization-defective J.D. cells GM-2408A. At 21 degrees and 28 degrees C, the diffusion fractions of approximately 75 and 60 percent, respectively, on both cell lines. The lipid analog nitrobenzoxadiazolephosphatidylcholine (NBD-PC) diffused in the GM-2408A cell membrane at 1.5x10(-8) cm(2)/sec at 22 degrees C. On blebs induced in GM-2408A cell membranes, the dil(3)-LDL receptor complex diffusion coefficient increased to approximately 10(-9) cm(2)/s, thus approaching the maximum theoretical predictions for a large protein in the viscous lipid bilayer. Cytoskeletal staining of blebs with NBD- phallacidin, a fluorescent probe specific for F-actin, indicated that loss of the bulk of the F-actin cytoskeleton accompanied the release of the natural constraints on later diffusion observed on blebs. This work shows that the internalization defect of J.D. is not due to immobilization of the LDL-receptor complex since its diffusibility is sufficient to sustain even the internalization rates observed in the native fibroblasts. Nevertheless, as with many other cell membrane receptors, the diffusion coefficient of the LDL-receptor complex is at least two orders of magnitude slower on native membrane than the viscous limit approached on cell membrane blebs where it is released from lateral constraints. However, LDL-receptor diffusion may not limit LDL internalization in normal human fibroblasts.

Actins↗

PubMed2005

Diffusion-tensor MR imaging of corticospinal tract in amyotrophic lateral sclerosis and progressive muscular atrophy.

PURPOSE: To prospectively evaluate several diffusion-tensor magnetic resonance (MR) imaging indexes (mean diffusivity [MD], fractional anisotropy [FA], and eigenvalues) of corticospinal tract impairment in patients with progressive muscular atrophy (PMA) and patients with amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: This study had institutional review board approval, and written informed consent was obtained from all subjects. Eight male patients with PMA (mean age, 63 years +/- 13 [standard deviation]), eighteen patients with ALS (14 men and four women; mean age, 64 years +/- 7), and twelve control subjects (four men and eight women; mean age, 65 years +/- 6) underwent diffusion-tensor MR imaging at which 25 spin-echo echo-planar imaging diffusion-weighted images (b = 1000 sec/mm2) were acquired along noncollinear directions. MD and FA were measured along the corticospinal tracts in each patient and subject. Changes in diffusion along and orthogonal to fiber bundles in patients were evaluated by using diffusion-tensor eigenvalues. Differences in diffusion-tensor imaging indexes between patients with PMA and those with ALS, as compared with these indexes in control subjects, were evaluated with Mann-Whitney testing. Correlations between diffusion-tensor imaging indexes and clinical variables were estimated with Pearson and Spearman rank correlation testing. RESULTS: As compared with MD (697.1 x 10(-6) mm2/sec +/- 28.1) and FA (0.585 +/- 0.032) in control subjects, MD was typically significantly increased (734.7 x 10(-6) mm2/sec +/- 41.2, P = .035) and FA significantly decreased (0.534 +/- 0.053, P = .037) along the corticospinal tracts in patients with ALS, while these parameters showed no significant change in patients with PMA (MD, 707.0 x 10(-6) mm2/sec +/- 44.2; FA, 0.559 +/- 0.028). Estimation of diffusion-tensor eigenvalues revealed normal diffusion along fiber tracts in all patients, while diffusion was increased orthogonal to fiber tracts only in patients with typical ALS. In patients with ALS, MD correlated with disease duration while FA correlated with disease severity. CONCLUSION: Diffusion-tensor MR imaging reveals corticospinal tract impairment in ALS but not in PMA.

Aged↗

PubMed2004

In vivo measurement of brain extracellular space diffusion by cortical surface photobleaching.

Molecular diffusion in the brain extracellular space (ECS) is an important determinant of neural function. We developed a brain surface photobleaching method to measure the diffusion of fluorescently labeled macromolecules in the ECS of the cerebral cortex. The ECS in mouse brain was labeled by exposure of the intact dura to fluorescein-dextrans (M(r) 4, 70, and 500 kDa). Fluorescein-dextran diffusion, detected by fluorescence recovery after laser-induced cortical photobleaching using confocal optics, was slowed approximately threefold in the brain ECS relative to solution. Cytotoxic brain edema (produced by water intoxication) or seizure activity (produced by convulsants) slowed diffusion by >10-fold and created dead-space microdomains in which free diffusion was prevented. The hindrance to diffusion was greater for the larger fluorescein-dextrans. Interestingly, slowed ECS diffusion preceded electroencephalographic seizure activity. In contrast to the slowed diffusion produced by brain edema and seizure activity, diffusion in the ECS was faster in mice lacking aquaporin-4 (AQP4), an astroglial water channel that facilitates fluid movement between cells and the ECS. Our results establish a minimally invasive method to quantify diffusion in the brain ECS in vivo, revealing stimulus-induced changes in molecular diffusion in the ECS with unprecedented spatial and temporal resolution. The in vivo mouse data provide evidence for: (1) dead-space ECS microdomains after brain swelling; (2) slowed molecular diffusion in the ECS as an early predictor of impending seizure activity; and (3) a novel role for AQP4 as a regulator of brain ECS.

Animals↗

PubMed2006

All-trans retinol in rod photoreceptor outer segments moves unrestrictedly by passive diffusion.

The visual pigment protein of vertebrate rod photoreceptors, rhodopsin, contains an 11-cis retinyl moiety that is isomerized to all-trans upon light absorption. Subsequently, all-trans retinal is released from the protein and reduced to all-trans retinol, the first step in the recycling of rhodopsin's chromophore group through the series of reactions that constitute the visual cycle. The concentration of all-trans retinol in photoreceptor outer segments can be monitored from its fluorescence. We have used two-photon excitation (720 nm) of retinol fluorescence and fluorescence recovery after photobleaching to characterize the mobility of all-trans retinol in frog photoreceptor outer segments. Retinol produced after rhodopsin bleaching moved laterally in the disk membrane bilayer with an apparent diffusion coefficient of 2.5 +/- 0.3 micro m(2) s(-1). The diffusion coefficient of exogenously added retinol was 3.2 +/- 0.5 micro m(2) s(-1). These diffusion coefficients are in close agreement with those reported for lipids, suggesting that retinol is not tightly bound to protein sites that would be diffusing much more slowly in the plane of the membrane. In agreement with this interpretation, a fluorescent-labeled C-16 fatty acid diffused laterally with a similar diffusion coefficient, 2.2 +/- 0.2 micro m(2) s(-1). Retinol also moved along the length of the rod outer segment, with an apparent diffusion coefficient of 0.07 +/- 0.01 micro m(2) s(-1), again suggesting that it is not tightly bound to proteins that would confine it to the disks. The axial diffusion coefficient of exogenously added retinol was 0.05 +/- 0.01 micro m(2) s(-1). In agreement with passive diffusion, the rate of axial movement was inversely proportional to the square of the length of the rod outer segment. Diffusion of retinol on the plasma membrane of the outer segment can readily account for the measured value of the axial diffusion coefficient, as the plasma membrane comprises approximately 1% of the total outer-segment membrane. The values of both the lateral and axial diffusion coefficients are consistent with most of the all-trans retinol in the outer segments moving unrestricted and not being bound to carrier proteins. Therefore, and in contrast to other steps of the visual cycle, there does not appear to be any specialized processing for all-trans retinol within the rod outer segment.

Animals↗

PubMed1983

Diffusion coefficients of CO2 molecule and bicarbonate ion in hemoglobin solution measured by fluorescence technique.

The diffusion process of CO2 within a thin layer of hemoglobin (Hb) solution was followed by pH-sensitive fluorescence of 4-methylumbelliferone. In the presence of sufficient carbonic anhydrase in the layer, the pH change was accelerated and determined only by the diffusion. The diffusion rate was reduced as the Hb concentration was increased. The pH rise observed in the CO2 diffusion out of the layer was slower than the pH fall caused by inward diffusion. However, the outward diffusion rate was faster than the inward diffusion rate in contrast to the pH change. The diffusion coefficients of molecular CO2 and bicarbonate ion were separately determined from the simulated and experimental PCO2-time curves by utilizing the non-linearity of the CO2 dissociation curve. The simulated curve was obtained from a numerical solution of the differential equation for diffusion by using the measured CO2 dissociation curve. The diffusion coefficient of CO2 was assumed to decrease exponentially with increasing Hb concentration. The diffusion coefficient of HCO3- was found to be reduced hyperbolically as the Hb concentration was increased. The diffusion coefficients of CO2 and HCO3- of 100% hemolysate were 0.34 X 10(-5) and 0.14 X 10(-5) cm2/sec, respectively.

Adult↗

PubMed2003

Line scan diffusion imaging of the spine.

BACKGROUND AND PURPOSE: Recent findings suggest that diffusion-weighted imaging might be an important adjunct to the diagnostic workup of disease processes in the spine, but physiological motion and the challenging magnetic environment make it difficult to perform reliable quantitative diffusion measurements. Multi-section line scan diffusion imaging of the spine was implemented and evaluated to provide quantitative diffusion measurements of vertebral bodies and intervertebral disks. METHODS: Line scan diffusion imaging of 12 healthy study participants and three patients with benign vertebral compression fractures was performed to assess the potential of line scan diffusion imaging of the spinal column. In a subgroup of six participants, multiple b-value (5-3005 s/mm(2)) images were obtained to test for multi-exponential signal decay. RESULTS: All images were diagnostic and of high quality. Mean diffusion values were (230 +/- 83) x 10(-6) mm(2)/s in the vertebral bodies, (1645 +/- 213) x 10(-6) mm(2)/s in the nuclei pulposi, (837 +/- 318) x 10(-6) mm(2)/s in the annuli fibrosi and ranged from 1019 x 10(-6) mm(2)/s to 1972 x 10(-6) mm(2)/s in benign compression fractures. The mean relative intra-participant variation of mean diffusivity among different vertebral segments (T10-L5) was 2.97%, whereas the relative difference in mean diffusivity among participants was 7.41% (P <.0001). The estimated measurement precision was <2%. A bi-exponential diffusion attenuation was found only in vertebral bodies. CONCLUSION: Line scan diffusion imaging is a robust and reliable method for imaging the spinal column. It does not suffer as strongly from susceptibility artifacts as does echo-planar imaging and is less susceptible to patient motion than are other multi-shot techniques. The different contributions from the water and fat fractions need to be considered in diffusion-weighted imaging of the vertebral bodies.

Adult↗

PubMedDate not supplied

Parenchymal abnormalities associated with cerebral venous sinus thrombosis: assessment with diffusion-weighted MR imaging.

BACKGROUND AND PURPOSE: The common entity cerebral venous sinus thrombosis is associated with the poorly characterized imaging finding of parenchymal abnormalities; diffusion-weighted imaging has offered some insight into these manifestations. We assessed the relationship between the diffusion constant from apparent diffusion coefficient (ADC) maps in patients with cerebral venous thrombosis (CVT) with follow-up imaging findings and clinical outcome. METHODS: We evaluated the medical records and T2-weighted MR images of 13 patients with CVT complicated by intraparenchymal abnormality. Diffusion-weighted (DW) images and ADC maps were evaluated for increased, decreased, or unchanged signal intensity and were compared with signal intensity of contralateral, normal-appearing brain. In addition, ADCs were obtained in nine pixel regions of interest in abnormal regions in eight of the 13 patients. RESULTS: Eight patients had superficial CVT, and five had superficial and deep CVT. CVT of deep veins was associated with deep gray nucleus and deep white matter abnormalities, whereas superficial CVT was associated with cortical and subcortical abnormalities. Twenty-four nonhemorrhagic lesions were identified in 10 of 13 patients on the basis of follow-up imaging findings. Four patients without seizures had lesions with decreased diffusion that appeared hyperintense on follow-up T2-weighted images, three patients with seizures had lesions with decreased diffusion that resolved, and seven patients had lesions with increased diffusion that resolved. Three of 10 patients had more than one lesion type. No difference was noted in mean ADCs for lesions with decreased diffusion that resolved compared with lesions with decreased diffusion that persisted. CONCLUSION: DW imaging in these patients disclosed three lesion types: lesions with elevated diffusion that resolved, consistent with vasogenic edema; lesions with low diffusion that persisted, consistent with cytotoxic edema in patients without seizure activity; and lesions with low diffusion that resolved in patients with seizure activity. This information may be important in prospectively determining severity of irreversible injury and in patient treatment.

Adolescent↗

PubMed1998

Turbo spin-echo diffusion-weighted MR of ischemic stroke.

PURPOSE: Our objective was to determine whether a multisection technique, diffusion-weighted half-Fourier single-shot turbo spin-echo (HASTE) imaging, can compensate for the drawbacks common to other diffusion-weighted techniques; specifically, the need for echo-planar technology and the presence of susceptibility artifacts in areas close to the skull base. METHODS: Forty subjects who were referred to the stroke service with signs of acute (less than 24 hour) neurologic dysfunction were included in this prospective study. MR imaging of the brain was performed with diffusion-weighted echo-planar and diffusion-weighted HASTE sequences. The images obtained with both sequences were analyzed for the presence of hyperintensities corresponding to ischemic lesions as well as for the presence of image artifacts and distortions. RESULTS: Diffusion-weighted HASTE images showed areas of hyperintensity corresponding to the infarcts present on diffusion-weighted echo-planar imaging studies without distortion or susceptibility artifacts in all the patients who had a stroke. Twelve patients had no acute ischemic lesions; of these, five had other findings, six had normal findings, and in one patient, a hyperintensity seen on diffusion-weighted echo-planar images proved to be an artifact on diffusion-weighted HASTE images. CONCLUSIONS: Diffusion-weighted HASTE is equal to diffusion-weighted echo-planar imaging in the detection of early ischemia. Because of the absence of significant image distortions and other artifacts, diffusion-weighted HASTE permits fast multiplanar imaging in artifact-prone regions, such as the posterior fossa and the inferior frontal and temporal lobes. Diffusion imaging can be performed on conventional systems with strengths of 1.5 T that do not have echo-planar imaging capabilities.

Acute Disease↗

PubMed1993

The role of mastectomy in patients with stage I-II breast cancer presenting with gross multifocal or multicentric disease or diffuse microcalcifications.

PURPOSE: Women with Stage I-II invasive breast cancer who present with gross multicentric disease or diffuse microcalcifications have a significant risk of breast recurrence when treated with conservative surgery and radiation. The purpose of this report is to present the results of mastectomy in this group of patients. METHODS AND MATERIALS: Between 1982 and 1989, 88 patients with clinical Stage I-II breast cancer who presented with clinical and mammographic evidence of gross multicentric disease or diffuse microcalcifications underwent modified radical mastectomy. Median followup was 4 years for the 57 patients with gross multicentric disease and 5.6 years for 31 patients with diffuse microcalcifications. At the time of mastectomy, 42% of patients were found to have positive axillary nodes. Following mastectomy, 15 patients received post mastectomy radiation and 35 patients received adjuvant systemic chemotherapy. RESULTS: When compared to a group of 1295 patients with unifocal, Stage I-II breast cancer, treated with conservative surgery and radiation during the same time period, patients with gross multicentric disease and diffuse microcalcifications had a significantly higher incidence of > or = 4 positive nodes, patients with gross multicentric disease had a lower incidence of positive resection margins following mastectomy and patients with diffuse microcalcifications were younger. The 5-year actuarial risk of an isolated local-regional recurrence was 8% for patients with gross multicentric disease or diffuse microcalcifications and 7% for patients with unifocal disease. Patients with gross multicentric disease or diffuse microcalcifications and > or = 4 positive axillary nodes who did not receive post mastectomy radiation had an increased risk for local regional recurrence. There were no significant differences in the 5-year actuarial overall or relapse-free survival (88% and 73% gross multicentric disease, 97% and 86% diffuse microcalcifications and 90% and 79% unifocal disease), freedom from distant metastasis (76% gross multicentric disease, 90% diffuse microcalcifications, 86% unifocal disease) or incidence of contralateral breast cancer (10% gross multicentric disease, 13% diffuse microcalcifications, 8% unifocal disease) among the three groups. CONCLUSION: The present study demonstrates no increased risk of local-regional recurrence in patients with gross multicentric disease or diffuse microcalcifications undergoing mastectomy in contrast to the increased risk of breast recurrence in patients with gross multicentric disease undergoing conservative surgery and radiation. Indications for post mastectomy radiation include > or = 4 positive nodes or close or positive surgical margins. Despite a significantly higher incidence of > or = 4 positive nodes, patients with gross multicentric disease and diffuse microcalcifications have a 5-year actuarial overall and relapse-free survival comparable to a group of patients with unifocal disease treated with conservative surgery and radiation.

Actuarial Analysis↗

PubMedDate not supplied

Random walk analysis of restricted metabolite diffusion in skeletal myofibril systems.

The purpose of this work was the development of a basal mathematical model for the diffusion of low-molecular metabolites in a skeletal muscle cell. A three-dimension diffusion of low-molecular particles was simulated by a Monte-Carlo method (random walks of diffusing molecules). The model takes into account the following structural elements: (i) a regular lattice of actin and myosin filaments inside a myofibril; (ii) the membranes of sarcoplasmic reticulum and mitochondria surrounding the myofibrils; (iii) a set of myofibrils inside a skeletal muscle cell. We simulated diffusion of particles in the bulk of intracellular water phase and their reflections from the rigid surfaces of intracellular structures. The model allowed to calculate the apparent coefficients of particle diffusion in the axial and radial directions, Dparallel(app) and Dperpendicular(app), respectively. In accordance with experimental data from literature, the coefficient Dparallel(app) was independent of time. The coefficient of radial diffusion Dperpendicular(app) decreased with time to steady state values similar to that determined by the NMR diffusion spectroscopy methods. The interactions of diffusing particles with thin and thick filaments of myofibrils could explain the decrease in the Dperpendicular(app) value by a factor of 20%. The collisions of particles with myofilaments began to reveal themselves as a gradual decrease in the Dperpendicular(app) value at early stages of diffusion (t1/2 approximately equal to 0.05 microsec). The contribution of particle reflections from the membranes of sarcoplasmic reticulum and mitochondria to the retardation of the radial diffusion was about of 20-30%, depending on porosity of a membranous shield around the myofibril. For conventional sizes of a membranous shield (diameter 2 microm), the interactions of particles with the shield caused a decrease in the Dperpendicular(app) value with a half-time t1/2 approximately equal to 0.5 msec. This time is essentially lower by a factor about of 100 than that found in published NMR measurements. When we considered diffusion of particles inside a cell compartment confined to impermeable membranous shield, the reflection of particles from this shield led the drastic decrease in the radial diffusion coefficient (Dperpendicular(app) --> porportional to when t --> porportional to). This pattern of the Dperpendicular(app)(t) time-course might be expected in the NMR measurements on skeletal muscle tissue where a sarcolemma represents an impermeable shield for ATP and PCr molecules.

Models, Theoretical↗

PubMed1995

Experimental allergic encephalomyelitis in non-human primates: diffusion imaging of acute and chronic brain lesions.

Diffusion imaging and T2-weighted magnetic resonance imaging were performed on 16 monkeys with experimental allergic encephalomyelitis (EAE), a model of the human demyelinating disease MS. The purpose of this study was to determine whether local changes in diffusion image intensity could be correlated with the formation of acute and chronic demyelinating lesions. Diffusion image analysis was restricted to the internal capsule of the brain because of its anatomic orientation of fiber pathways. Acute inflammatory EAE lesions were large and monophasic, as visualized by T2-weighted MRI, and were accompanied by a decrease in the diffusion MR image signal with the diffusion-sensitizing gradient in all three orthogonal directions (n = 27 brain regions, P < 0.005). Chronic demyelinating lesions were preceded by multiple inflammatory attacks, as visualized by MRI, and by a decrease in diffusion MR image signal with the diffusion-sensitizing gradient in the two orthogonal directions perpendicular to the fibers of the internal capsule (n = 18 brain regions, P < 0.005). However, for the chronic group, there was no significant change in the diffusion MR image signal with diffusion-sensitizing gradient parallel to the fibers of the internal capsule at the terminal scan, suggesting little change in the water diffusion within the nerve fibers. These results suggest that diffusion imaging holds promise for measuring subtle changes in water diffusion due to different types of brain damage.

Acute Disease↗

PubMed2003

Holographic diffuser by use of a silver halide sensitized gelatin process.

Diffusers play an important role in liquid crystal display (LCD) application as a beam-shaping device, a brightness homogenizer, a light-Scattering device, and an imaging screen. The transmittance and diffusing angle of the diffusers are the critical aspects for the applications to the LCD. The holographic diffusers by use of various processing methods have been investigated. The diffusing characteristics of different diffusing materials and processing methods have been evaluated and compared. The microstructures of holographic diffuse have been investigated by use of using scanning electron microscopy. The holographic diffusers by use of the silver halide sensitized gelatin (SHSG) method have the structural merits for the improvement of the quality of diffusers. The features of holographic diffuser were exceptional in terms of transmittance and diffusing angle. The replication method by use of the SHSG process can be directly used for the manufacturing of diffusers for the display application.

Journal Article↗

PubMed2001

Microstructural brain development after perinatal cerebral white matter injury assessed by diffusion tensor magnetic resonance imaging.

OBJECTIVE: Brain injury in premature infants is characterized predominantly by perinatally acquired lesions in the cerebral white matter (WM). The impact of such injury on the subsequent development of cerebral WM is not clear. This study uses diffusion tensor magnetic resonance imaging (MRI) to evaluate the effects of cerebral WM injury on subsequent microstructural brain development in different WM areas of the brain. METHODS: Twenty premature infants (gestational age: 29.1 +/- 1.9 weeks) were studied by conventional MRI within the first 3 weeks of life and again at term, with the addition at the latter time of diffusion tensor MRI. Ten of the preterm infants had cerebral WM injury identified by the early MRI and were matched with 10 premature infants of similar gestational age and neonatal course but with normal neonatal MRI scans. Diffusion tensor MRI at term was acquired in coronal and axial planes and used to determine the apparent diffusion coefficient, a measure of overall restriction to water diffusion, and the relative anisotropy (RA), a measure of preferred directionality of diffusion, in central WM, anterior frontal WM, occipital WM, temporal WM, and the posterior limb of the internal capsule. Diffusion vector maps were generated from the diffusion tensor analysis to define the microstructural architecture of the cerebral WM regions. RESULTS: At term, the diffusion tensor MRI revealed no difference in apparent diffusion coefficient among preterm infants with or without perinatal WM lesions. By contrast, RA, the measure of preferred directionality of diffusion and thereby dependent on development of axonal fibers and oligodendroglia, was 25% lower in central WM, the principal site of the original WM injury. However, RA was unaffected in relatively uninjured WM areas, such as temporal, anterior frontal, and occipital regions. Notably, RA values in the internal capsule, which contains fibers that descend from the injured cerebral WM, were 20% lower in the infants with WM injury versus those without. Diffusion vector maps showed striking alterations in the size, orientation, and organization of fiber tracts in central WM and in those descending to the internal capsule. CONCLUSIONS: Perinatal cerebral WM injury seems to have major deleterious effects on subsequent development of fiber tracts both in the cerebral WM and more distally. The ultimate impact of brain injury in the newborn should be considered as a function not only of tissue destruction, but also of impaired subsequent brain development.

Humans↗

PubMed2001

Diffusion tensor imaging of patients with HIV and normal-appearing white matter on MR images of the brain.

BACKGROUND AND PURPOSE: HIV enters the CNS early in the course of infection and produces neuropsychiatric impairment throughout the course of illness, which preferentially affects the subcortical white matter. The development of a neuroimaging marker of HIV may allow for the earliest detection of cognitive impairment. The purpose of this study was to determine whether MR diffusion tensor imaging can detect white matter abnormalities in patients who have tested positive for HIV. METHODS: Ten patients with HIV (eight men and two women; mean age, 42 years) underwent MR imaging of the brain with MR diffusion tensor imaging, which included routine fluid-attenuated inversion recovery and fast spin-echo T2-weighted imaging. Diffusion constants and anisotropy indices were calculated from diffusion tensor maps. Peripheral viral load, Centers for Disease Control staging, and cluster of differentiation 4 levels were determined. RESULTS: All patients had normal results of MR imaging of the brain, except for mild atrophy. Four of 10 patients had undetectable viral loads. These patients were receiving highly active antiretroviral therapy. The diffusion constant and anisotropy were normal. Four of 10 patients had viral loads between 10,000 and 200,000. Diffusion anisotropy in the splenium and genu was significantly decreased (P < .02). The diffusion constant of the subcortical white matter was elevated in the frontal and parietooccipital lobes (11%). Two of 10 patients had viral loads >400,000. Anisotropy of the splenium was half normal (P < .0004) and of the genu was decreased 25% (P < .002). The average diffusion constant was diffusely elevated in the subcortical white matter. CONCLUSION: Calculating the diffusion constant and anisotropy in the subcortical white matter and corpus callosum in patients with HIV detected abnormalities despite normal-appearing white matter on MR images and nonfocal neurologic examinations. Patients with the highest diffusion constant elevations and largest anisotropy decreases had the most advanced HIV disease. Patients with the lowest viral load levels, who had normal anisotropy and diffusion constants, were receiving highly active antiretroviral therapy.

Adult↗

PubMed2005

A model for diffusion in white matter in the brain.

Diffusion of molecules in brain and other tissues is important in a wide range of biological processes and measurements ranging from the delivery of drugs to diffusion-weighted magnetic resonance imaging. Diffusion tensor imaging is a powerful noninvasive method to characterize neuronal tissue in the human brain in vivo. As a first step toward understanding the relationship between the measured macroscopic apparent diffusion tensor and underlying microscopic compartmental geometry and physical properties, we treat a white matter fascicle as an array of identical thick-walled cylindrical tubes arranged periodically in a regular lattice and immersed in an outer medium. Both square and hexagonal arrays are considered. The diffusing molecules may have different diffusion coefficients and concentrations (or densities) in different domains, namely within the tubes' inner core, membrane, myelin sheath, and within the outer medium. Analytical results are used to explore the effects of a large range of microstructural and compositional parameters on the apparent diffusion tensor and the degree of diffusion anisotropy, allowing the characterization of diffusion in normal physiological conditions as well as changes occurring in development, disease, and aging. Implications for diffusion tensor imaging and for the possible in situ estimation of microstructural parameters from diffusion-weighted MR data are discussed in the context of this modeling framework.

Algorithms↗

PubMed2007

Redox-stratification controlled biofilm (ReSCoBi) for completely autotrophic nitrogen removal: the effect of co- versus counter-diffusion on reactor performance.

A multi-population biofilm model for completely autotrophic nitrogen removal was developed and implemented in the simulation program AQUASIM to corroborate the concept of a redox-stratification controlled biofilm (ReSCoBi). The model considers both counter- and co-diffusion biofilm geometries. In the counter-diffusion biofilm, oxygen is supplied through a gas-permeable membrane that supports the biofilm while ammonia (NH(4)(+)) is supplied from the bulk liquid. On the contrary, in the co-diffusion biofilm, both oxygen and NH(4)(+) are supplied from the bulk liquid. Results of the model revealed a clear stratification of microbial activities in both of the biofilms, the resulting chemical profiles, and the obvious effect of the relative surface loadings of oxygen and NH(4)(+) (J(O(2))/J(NH(4)(+))) on the reactor performances. Steady-state biofilm thickness had a significant but different effect on T-N removal for co- and counter-diffusion biofilms: the removal efficiency in the counter-diffusion biofilm geometry was superior to that in the co-diffusion counterpart, within the range of 450-1,400 microm; however, the efficiency deteriorated with a further increase in biofilm thickness, probably because of diffusion limitation of NH(4)(+). Under conditions of oxygen excess (J(O(2))/J(NH(4)(+)) > 3.98), almost all NH(4)(+) was consumed by aerobic ammonia oxidation in the co-diffusion biofilm, leading to poor performance, while in the counter-diffusion biofilm, T-N removal efficiency was maintained because of the physical location of anaerobic ammonium oxidizers near the bulk liquid. These results clearly reveal that counter-diffusion biofilms have a wider application range for autotrophic T-N removal than co-diffusion biofilms.

Ammonia↗

PubMed2004

Analytical error propagation in diffusion anisotropy calculations.

PURPOSE: To develop an analytical formalism describing how noise and selection of diffusion-weighting scheme propagate through the diffusion tensor imaging (DTI) computational chain into variances of the diffusion tensor elements, and errors in the relative anisotropy (RA) and fractional anisotropy (FA) indices. MATERIALS AND METHODS: Singular-value decomposition (SVD) was used to determine the tensor variances, with diffusion-weighting scheme and measurement noise incorporated into the design matrix. Anisotropy errors were then derived using propagation of error. To illustrate the applications of the model, 12 data sets were acquired from each human subject, over a range of b-values (500-2500 seconds/mm2) and diffusion-weighting gradient directions (N = 6-55). The mean RA and FA values and their respective errors were calculated within a region of interest (ROI) in the splenium. The RA and FA errors as a function of b-value and N were evaluated, and a number of diffusion-weighting schemes were assessed based on a new metric, sum of diffusion tensor variances. RESULTS: When the acquisition time was held constant, the sum of the diffusion tensor variances decreased as N increased. The same trend was also observed for several diffusion-weighting schemes with constant condition number when noise in the diffusion-weighted (DW) images was assumed unity. Errors in both FA and RA increased with b-value and decreased with N. The FA error in the splenium was approximately threefold smaller than RA error, irrespective of b-value or N. CONCLUSION: The condition number may not adequately characterize the noise sensitivity for a given diffusion-weighting scheme. Signal averaging may not be as effective as increasing N, especially when N is small (e.g., N < 13). Due to its smaller error, FA is preferred over RA for quantitative DTI applications.

Adult↗