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PubMed2001

Mean diffusivity and fractional anisotropy histograms of patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Compared with conventional T2-weighted MR imaging, diffusion tensor MR imaging provides quantitative indices with increased specificity to the most destructive aspects of multiple sclerosis. In this study, we obtained brain mean diffusivity (_D) and fractional anisotropy histograms of patients with multiple sclerosis to compare them with those of healthy volunteers and to investigate the correlation between diffusion tensor MR imaging histogram-derived measures and the level of disability and quantities derived from conventional MR imaging. METHODS: Dual-echo and diffusion tensor MR images were obtained from 78 patients with relapsing-remitting, secondary progressive, or primary progressive multiple sclerosis and from 20 healthy control volunteers. After obtaining mean diffusivity (_D) and fractional anisotropy images and image coregistration, _D and fractional anisotropy histograms were created. From each histogram, the following measures were derived: the average _D and fractional anisotropy, the histogram peak heights, and the histogram peak locations. RESULTS: All the _D and fractional anisotropy histogram-derived measures were different between patients and controls at a significance level of P <.001. No differences were found in any of the considered quantities among the three multiple sclerosis phenotypes. In patients with relapsing-remitting multiple sclerosis, disability was correlated with histogram average_D (r = 0.4, P =.01) and peak height (r = -0.4, P =.01). In patients with secondary progressive multiple sclerosis, disability was correlated with fractional anisotropy histogram peak position (r = -0.6, P =.01). Significant correlations were also found between T2 lesion load and various diffusion tensor MR quantities. CONCLUSION: This study shows that brain _D and fractional anisotropy histograms are different for patients with multiple sclerosis compared with control volunteers. This study also shows that quantities derived from diffusion tensor MR imaging are correlated with disability in patients with relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis, suggesting that they might serve as additional measures of outcome when monitoring multiple sclerosis evolution in these patients.

Adult↗

PubMed2001

[Diffusion-weighted echo-planar sequences for the evaluation of the upper abdomen: technique optimization].

PURPOSE: To optimize the technique for the evaluation of molecular diffusion in the abdomen. MATERIAL AND METHODS: Fifteen healthy volunteers, 6 males and 9 females, ranging in age between 24 and 31 years underwent an MRI evaluation of the upper abdomen, using a superconductive 1.5T magnet (maximum gradient strength, 25 mT/m; minimum rise time 600 ms), equipped with phased array abdominal multicoil. Diffusion study was performed with a single-shot Inversion Recovery Spin-Echo Echo-planar sequence (IR-SE-EPI) with the following parameters: TR = infinite; TE=101 ms; matrix 128 yen 128; receiver bandwidth 2080 Hz/pixel; slices: n.20; slice thickness: 8 mm; acquisition time: 5.41 s. For diffusion weighting the following b values were employed: b=30 mm/s2, b=300 mm/s2 e b=500 mm/s2. Both qualitative and quantitative (calculation of linear regression analysis and of apparent diffusion coefficient) image analysis was performed. RESULTS: Image quality was graded as diagnostic in all the cases. Image quality decreased with the increase of b values: at low b values, the anatomy of upper abdominal organs was easily recognized, whereas, at high b values, the same organs could not be adequately assessed unless the images were compared with those obtained with low b values. Magnetic susceptibility artifacts were observed in all the cases; no significant chemical-shift artifacts were observed as the fat saturation pre-pulse was employed. Quantitative analysis demonstrated an apparent diffusion coefficient of 1.58 s/mm2 for the liver, 1.61 s/mm2 for the spleen and 5,14 s/mm2 for the gallbladder. A statistically significant difference (p<0.001) was observed between parenchymatous organs (liver and spleen) and gallbladder, presenting as a stationary fluid. CONCLUSIONS: Diffusion-weighted MR sequences may be implemented for abdominal studies, but the optimization of same parameters is slightly different compared with neuroradiologic applications. The potential applications are interesting above all as regards the characterization of focal liver lesions. Further developments are awaited in both sequence optimization (greater stability and lower sensitivity to magnetic susceptibility artifacts) and data analysis, with more complex algorithms able to better quantify the real diffusion coefficient.

Abdomen↗

PubMed2001

Visualization of nonstructural changes in early white matter development on diffusion-weighted MR images: evidence supporting premyelination anisotropy.

BACKGROUND AND PURPOSE: Previously, we showed that diffusion-weighted MR imaging depicts evidence of directionally preferential water motion in white matter structures of developing rat brain before and after myelination, and considerably earlier than conventional imaging strategies. Present data augment these imaging and corresponding histologic findings with electron-microscopic corroboration. We additionally report the findings of a 10-day-old rat pup tested functionally by administration of the sodium-channel blocker, tetrodotoxin. METHODS: In two rat pups, drawn from the population reported previously, MR estimates of diffusion anisotropy of the optic nerves and chiasm were compared with histologic and electron microscopy results. To test the hypothesis that "premyelination" directional preference of water motion in white matter structures relates to sodium-channel activity, MR imaging was performed in a 10-day-old rat pup treated with the sodium-channel blocker, tetrodotoxin, and findings were compared with data from an age-matched control. RESULTS: Although diffusion anisotropy was present in optic structures of the youngest animal, myelin-sensitive histologic staining did not show myelin before 12 days; electron microscopy confirmed lack of any myelin or its precursors during the earliest maturational stage. Administration of tetrodotoxin to the 10-day-old rat-pup led to loss of diffusion anisotropy. CONCLUSION: Our findings provide two pieces of supporting data for the hypothesis that nonstructural changes are responsible for early anisotropic diffusion: electron microscopy shows no evidence of myelin despite diffusion anisotropy, and inhibiting the sodium-channel pump appears to remove the directional preference of water motion. Visualization of nonstructural "premyelination" consequences with diffusion-weighted imaging emphasizes its sensitivity and potential in studying early processes of brain development.

Aging↗

PubMed1999

[Influence of decocting time on the amount of anthraguinone diffused from Cassia seeds].

OBJECTIVE: To study the influence of decocting time on the amount of anthraquinone diffused from the cassia seeds. METHOD: The amount of anthraquinone in the decoctions made in different lengths of decocting time was determined by spectrophotometry (for intact seeds and powdered seeds). RESULT: Fast nonlinear diffusion district, slow linear diffusion district and ceasing diffusion district were shown on the light absorption-decocting time curves, and appropriate smashing of the cassia seed facilitated the diffusion of anthraquinone. CONCLUSION: The best decocting time for anthraquinone to diffuse from the cassia seeds should be the ending time of the fast nonlinear diffusion district, while the second decoction should not be given up.

Anthraquinones↗

PubMedDate not supplied

Differences in the density and spatial distribution of florid and diffuse plaques in variant Creutzfeldt-Jakob disease (vCJD).

OBJECTIVE: To determine whether in cases of variant Creutzfeldt-Jakob disease (vCJD), the florid-type plaques are derived from the diffuse plaques or whether the 2 plaque types develop independently. MATERIAL: Blocks of frontal, parietal, occipital and temporal neocortex and cerebellar cortex from 11 cases of vCJD. METHOD: The density, distribution and spatial pattern of the florid and diffuse plaques were determined in each brain region using spatial pattern analysis. RESULTS: The density of the diffuse plaques was significantly greater than that of the florid plaques in most areas. The ratio of the diffuse to florid plaques varied between brain regions and was maximal in the molecular layer of the cerebellum. The densities of the florid and diffuse plaques were positively correlated in the parietal cortex, occipital cortex, the inferior temporal gyrus and the dentate gyrus. Plaque densities were not related to disease duration. In the cerebral cortex, the diffuse plaques were more commonly evenly distributed or occurred in large clusters along the cortex parallel to the pia mater compared with the florid plaques which occurred more frequently in regularly distributed clusters. CONCLUSION: The florid plaques may not be derived from the diffuse plaques, the 2 plaque types appearing to develop independently with unique factors involved in their pathogenesis.

Adolescent↗

PubMed1984

Combination chemotherapy for advanced non-Hodgkin's lymphomas other than diffuse histiocytic or undifferentiated histologies.

A combination chemotherapy program using methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (M-BACOD), which resulted in a high complete response rate and prolonged disease-free survival in lymphomas of the unfavorable diffuse histiocytic and diffuse undifferentiated histopathologic subgroups, was administered to 44 patients with advanced favorable and intermediate-prognosis non-Hodgkin's lymphomas, including nodular lymphoma of the poorly differentiated lymphocytic, mixed, and histiocytic subtypes, and diffuse lymphoma of the poorly differentiated lymphocytic or mixed histologic subtypes. High-dose methotrexate (3 g/m2) was given on Day 14 between cycles of bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone, administered every 3 weeks for ten cycles. Leucovorin factor (10 mg/m2) was given iv 24 hours after the methotrexate infusion was completed, and was continued at 10 mg/m2 by mouth every 6 hours for 72 hours. Therapy was well-tolerated, with predictable myelosuppression in the majority of patients. The complete response rate was 57% (25 of 44 patients), including ten of 18 (56%) patients with nodular and 15 of 26 (58%) patients with diffuse lymphomas. Median overall follow-up among living patients is 65 months, 58 months for patients with nodular and 69 months for patients with diffuse histologic subgroups. Overall survival at 5 years was 64% for patients who achieved complete response, 32% for partial responders, and 0% for those patients who did not respond. Disease-free survival of complete responders was 43% at 5 years, with only one disease-related death noted after 36 months. The nodular and diffuse patient subgroups had similar overall and disease-free survivals. Although initial bone marrow involvement was documented in nine of 18 (50%) nodular patients and in 13 of 26 (50%) diffuse patients, CNS relapse occurred in only one complete and two partial responders. The prolonged disease-free survival observed after M-BACOD therapy demonstrates that durable responses can be achieved with intensive chemotherapy.

Adolescent↗

PubMed1993

[Diffusion weighted magnetic resonance imaging in multiple cerebral infarction].

Serial examination of magnetic resonance images (MRI) for two months were carried out on two cases of multiple cerebral infarction during the acute stage. The T2-weighted MR images at the onset of the infarction showed both acute (new) and chronic (old) lesions appearing as high signal area. While on the diffusion weighted images only an acute lesion was detected as a high signal area with good contrast. The diffusion coefficient of the acute lesion was lower than that of normal white matter. Diffusion coefficient of the chronic lesions were higher than that of normal white matter. Therefore, on the apparent diffusion coefficient mapping images (ADC images) only an acute lesion appeared as a low signal area. The examination of diffusion images was very useful for distinguishing an acute lesion from a chronic lesion during the acute stage of multiple infarction. The diffusion weighted images after 4 weeks from the onset showed the diffusion coefficient of the "acute" lesion to be the same level of normal white matter. And after 8 weeks from the onset, increased to a level higher than that of normal white matter to the same level of the "chronic" lesion.

Aged↗

PubMed1995

Use of an enhanced gradient system for diffusion MR imaging with motion-artifact reduction.

PURPOSE: A spin-echo diffusion-sensitized pulse sequence using high gradients (23 mT/m) is introduced. MATERIAL AND METHODS: In order to minimize motion artefacts, velocity-compensating gradients, ECG-triggering and post-processing with phase correction and raw data averaging using navigator echoes was performed. The in vitro ratio of diffusion coefficients for water and acetone was determined and the water self-diffusion coefficient at different temperatures was evaluated. The pulse sequence was tested in 7 healthy volunteers and in 2 tumour patients with astrocytomas of grades I-II and III-IV. Both single-slice and multi-slice techniques were used. RESULTS: The incorporation of phase correction clearly improved the quality of both diffusion-encoded images and the calculated diffusion maps. Mean values of the diffusion coefficients in vivo were for CSF 2.66 x 10(-9) m2/s and for white and grey matter 0.69 x 10(-9) m2/s and 0.87 x 10(-9) m2/s, respectively. CONCLUSION: Velocity-compensating gradients in combination with a high gradient strength were shown to be useful for in vivo diffusion MR imaging.

Adult↗

PubMed1996

[Diffusion MRI study of cerebral white matter lesions in patients with Binswanger's disease].

We performed diffusion MRI studies in 14 patients with extensive ischemic leukoencephalopathy, including 9 with dementia (diagnosed as Binswanger's disease), and 5 without dementia, and 8 age-matched controls. Apparent diffusion coefficients (ADCs) in anterior and posterior periventricular white matter were significantly higher in demented and non-demented patients than in the controls, and diffusion anisotropy disappeared in patients because of the high ratio of the diffusion coefficients perpendicular to the nerve fibers to those parallel to the nerve fibers. ADCs in the corpus callosum were significantly higher in demented patients that in non-demented patients and controls. Therefore, diffusion anisotropy disappeared only in demented (Binswanger's disease) patients. These results suggest that the cerebral white matter lesions in Binswanger's disease reflect a decrease of nerve fibers and diffuse myelin loss, and that the loss of nerve fibers in the corpus callosum may play a role in inducing cognitive decline. Diffusion MRI may be useful in the pathophysiological evaluation of cerebral white matter lesions.

Aged↗

PubMed1997

Localized and diffuse ovarian cancer: is it the same entity?

In order to confront the question whether localized and diffuse ovarian cancers are the extremes of the same disease or two different entities, we compared anamnestic, intraoperative and laboratory findings, as well as the outcome. Sixty-four patients with invasive epithelial ovarian cancer were treated in our department between 1984-1991. After excluding patients with incomplete data, 59 women were finally included in the analysis. The patients were divided retrospectively into two groups according to the extent of the disease observed during the primary surgery. Disease confined to the ovaries was defined as localized form, and any other extraovarian involvement was defined as diffuse form. Twenty patients had localized (Group I), and 39 had diffuse disease (Group II). Comparing the two groups, no difference was observed concerning patient age, the age of menarche and menopause, gravity and parity, the percentage of smoking and hypertensive women, and the histologic type of the ovarian tumor. On the other hand, significant differences were obtained concerning the positive family history of cancer in localized versus diffused disease (10% versus 41%) (p < 0.04), the size of the tumor involving the ovaries (16.2 +/- 5.4 cm versus 7.0 +/- 3.1 cm) (p < 0.0001), the unilateral as opposed to bilateral disease (p < 0.0001), the volume of ascitic fluid (p < 0.002) and the histologic grade (p < 0.02). Laboratory parameters, including CA-125, serum albumin, total protein and lactate dehydrogenase differed significantly comparing the localized and diffused disease (p < 0.04, p < 0.0001, p < 0.003, p < 0.05, respectively). The median survival rate was significantly higher (p < 0.001) in patients with localized versus diffused disease. Our results support the concept that localized and diffused forms of ovarian cancer are probably two different entities.

Adult↗

PubMed1999

Discrepant expression of neprilysin on fibroblasts in diffuse systemic sclerosis.

OBJECTIVE: Neprilysin (NEP; EC3.4.24.11) is an ectopeptidase mainly produced by fibroblasts and cleaving a large number of neuropeptides. We previously found increased plasma circulating levels of NEP in patients with systemic sclerosis (SSc), but in SSc fibroblasts derived from the diffuse subset NEP was present in lower concentration. We evaluate in vitro fibroblasts of both subsets of the disease, diffuse and limited, the intracellular levels of NEP, and its expression as CD10 on the cellular surface. METHODS: Fibroblasts, derived from biopsies taken from affected skin of 8 patients with the limited subset and 5 with the diffuse subset, were grown in vitro and intracellular levels of NEP activity were measured with a fluorometric method, while CD10 surface expression was evaluated by FACS analysis. Cell proliferation was assessed by 3HThymidine incorporation. RESULTS: Intracellular NEP activity was significantly increased in diffuse (7.02+/-4.8 pg/ml/min 10(6) cells) compared to limited SSc (1.11+/-2.0) and control fibroblasts (1.41+/-0.9). CD10 expression was significantly impaired on diffuse SSc fibroblasts (47.3+/-15%) compared to controls (74.6+/-11%) and the limited subset (82.7+/-11%). Cell proliferation of diffuse SSc fibroblasts was strikingly higher than controls and limited SSc fibroblasts. CONCLUSION: These results confirm that NEP is produced by fibroblasts and indicate that in diffuse SSc fibroblasts NEP is produced in higher quantities, while the expression of the enzyme on the cell surface is significantly reduced. This condition may affect the proliferation rate of fibroblasts as well as the metabolism of various peptides.

Cell Division↗

PubMed2006

Age effects on diffusion tensor magnetic resonance imaging tractography measures of frontal cortex connections in schizophrenia.

Diffusion tensor magnetic resonance imaging (DT-MRI) has previously been used to investigate white matter tracts in schizophrenia, with inconsistent results. The aim of the study was to use a novel method for tract-specific measurements of fronto-temporal fasciculi in early-onset schizophrenia. We hypothesized that by making tract-specific measurements, clear diffusion abnormalities would be revealed in specific fasciculi in schizophrenia. Measurements of diffusion anisotropy and mean diffusivity were localized within fronto-temporal fasciculi by forming 3-D reconstructions of the cingulum, uncinate, superior longitudinal, and inferior fronto-occipital fasciculi using diffusion tensor tractography. We were limited in our ability to test our hypothesis by the important and surprising finding that age affected DT-MRI-based measures in schizophrenia patients in a different way from comparison subjects, most notably in the left superior longitudinal fasciculus. The youngest schizophrenia patients that we studied had lower diffusion anisotropy than age-matched comparison subjects, but this difference diminished with increasing age. The main conclusion of this study was that direct comparisons of absolute DT-MRI-based measures between individuals with schizophrenia and comparison subjects may be problematic and misleading because of underlying age-related differences in brain maturation between groups.

Adult↗

PubMed2003

An image-based finite difference model for simulating restricted diffusion.

Water diffusion in tissues is generally restricted and often anisotropic. Neural tissue is of particular interest, since it is well known that injury alters diffusion in a characteristic manner. Both Monte Carlo simulations and approximate analytical models have previously been reported in attempts to predict water diffusion behavior in the central nervous system. These methods have relied on axonal models, which assume simple geometries (e.g., ellipsoids, cylinders, and square prisms) and ignore the thickness of the myelin sheath. The current work describes a method for generating models using synthetic images. The computations are based on a 3D finite difference (FD) approximation of the diffusion equation. The method was validated with known analytic solutions for diffusion in a cylindrical pore and in a hexagonal array of cylinders. Therefore, it is envisioned that, by exploiting histologic images of neuronal tissues as input model, current method allows investigating the water diffusion behavior inside biological tissues and potentially assessing the status of neural injury and regeneration.

Axons↗

PubMedDate not supplied

The basis of anisotropic water diffusion in the nervous system - a technical review.

Anisotropic water diffusion in neural fibres such as nerve, white matter in spinal cord, or white matter in brain forms the basis for the utilization of diffusion tensor imaging (DTI) to track fibre pathways. The fact that water diffusion is sensitive to the underlying tissue microstructure provides a unique method of assessing the orientation and integrity of these neural fibres, which may be useful in assessing a number of neurological disorders. The purpose of this review is to characterize the relationship of nuclear magnetic resonance measurements of water diffusion and its anisotropy (i.e. directional dependence) with the underlying microstructure of neural fibres. The emphasis of the review will be on model neurological systems both in vitro and in vivo. A systematic discussion of the possible sources of anisotropy and their evaluation will be presented followed by an overview of various studies of restricted diffusion and compartmentation as they relate to anisotropy. Pertinent pathological models, developmental studies and theoretical analyses provide further insight into the basis of anisotropic diffusion and its potential utility in the nervous system.

Anisotropy↗

PubMed2002

Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water.

Myelin loss and axonal damage are both observed in white matter injuries. Each may have significant impact on the long-term disability of patients. Currently, there does not exist a noninvasive biological marker that enables differentiation between myelin and axonal injury. We describe herein the use of magnetic resonance diffusion tensor imaging (DTI) to quantify the effect of dysmyelination on water directional diffusivities in brains of shiverer mice in vivo. The principal diffusion eigenvalues of eight axonal fiber tracts that can be identified with certainty on DTI maps were measured. The water diffusivity perpendicular to axonal fiber tracts, lambda(perpendicular), was significantly higher in shiverer mice compared with age-matched controls, reflecting the lack of myelin and the increased freedom of cross-fiber diffusion in white matter. The water diffusivity parallel to axonal fiber tracts, lambda(parallel), was not different, which is consistent with the presence of intact axons. It is clear that dysmyelination alone does not impact lambda(parallel). The presence of intact axons in the setting of incomplete myelination was confirmed by electron microscopy. Although further validation is still needed, our finding suggests that changes in lambda(perpendicular) and lambda(parallel) may potentially be used to differentiate myelin loss versus axonal injury.

Animals↗

PubMed1993

Effect of the bathing fluid on measurements of diffusion in dental plaque.

The suggestion that loss of labile components from dental plaque into contacting aqueous buffer during some diffusion measurements might change the plaque's diffusion behaviour, and therefore invalidate the results, has been tested using tracer clearance. (a) Diffusion of [14C]-acetate and 3H2O was determined before and after a 3-4 h equilibration with neutral buffer. No differences or trends were found. (b) Mean normalized [14C]-acetate clearance curves from live plaque for measurements before and after such equilibration were identical in shape and showed no change in diffusion coefficient during clearance, as evidenced by their fits to the theoretical clearance curve. No significant difference was found between coefficients for the two periods (paired sample test). In addition, [14C]-lactate and 3H2O were found to permeate plaque in a miniature diaphragm diffusion cell at rates independent of whether the plaque was bathed either in saliva supernatant, plaque fluid or neutral buffer. This lent some further support to the main findings. It is concluded that diffusion through dental plaque is little affected by the bathing fluid.

Biological Transport↗

PubMed2006

Investigation of multicomponent diffusion in cat brain using a combined MTC-DWI approach.

In this study, multiple-component water diffusion in the cat brain is investigated using an approach that combines diffusion-weighted images using multiple b values with magnetization transfer contrast (MTC). The MTC allows filter of signal originating from water molecules that rapidly exchange with binding sites on large macromolecular structures, and in brain white matter, it is assumed that a significant portion of the MTC is due to the interaction of water with the extraaxonal myelin sheath. Henceforth, multicomponent analysis of diffusion curves with and without MTC may shed light on the contribution of the extraaxonal water to the diffusion signal and on the relationship between diffusion components and tissue compartments in the brain. When a biexponential model was applied to the data, the volume fractions of the two diffusion components changed significantly in white matter with the application of the MTC. These changes are then discussed in the frame of tissue components and the possible interaction with the myelin sheath.

Animals↗

PubMed2005

Pattern of diffusion disturbance related to clinical diagnosis: The K(CO) has no diagnostic value next to the DL(CO).

AIM OF THE STUDY: The diffusion capacity of the lung for carbon monoxide (DL(CO)) is an important tool in the diagnosis and follow-up of patients with pulmonary diseases. In case of a decreased DL(CO) the K(CO), defined as DL(CO)/V(A) (V(A) is alveolar volume), can differentiate between normal alveolocapillary membrane (normal K(CO)) and abnormal alveolocapillary membrane (low K(CO)). The latter category consists of decreased surface of the membrane, increased thickness or decreased perfusion of ventilated alveoli. The V(A)/TLC (TLC is total lung capacity determined by whole body plethysmography) can partially differentiate between these categories. The aim of this study was to investigate the diagnostic value of the specific diffusion disturbances, which can be constructed by combining the DL(CO), K(CO) and V(A)/TLC. METHODS: In 460 patients the diagnosis made by clinicians were fitted into five diagnostic categories: asthma, chronic obstructive pulmonary disease (COPD), treatment effects of haematologic malignancies, heart failure and diffuse parenchymal lung diseases (DPLD). These categories were linked to the pattern of diffusion disturbance. RESULTS: Almost all patients with asthma have a normal DL(CO), most patients in the other groups do not have the expected pattern of diffusion disturbance, especially in the group with DPLD a bad match is observed. CONCLUSION: In this study the pattern of diffusion disturbance is of limited use in establishing a diagnosis. The use of the K(CO) next to the DL(CO) has no additional diagnostic value. Regional ventilation-perfusion inequality probably forms an important underlying mechanism of decreased DL(CO).

Adolescent↗