Topography of brain sodium accumulation in progressive multiple sclerosis

Object

Sodium accumulation is involved in neuronal injury occurring in multiple sclerosis (MS). We aimed to assess sodium accumulation in progressive MS, known to suffer from severe neuronal injury.

Materials and methods

3D-²³Na-MRI was obtained on a 3T-MR-scanner in 20 progressive MS patients [11 primary-progressive (PPMS) and nine secondary-progressive (SPMS)] and 15 controls. Total sodium concentrations (TSC) within grey matter (GM), normal-appearing white matter (WM) and lesions were extracted. Statistical mapping analyses of TSC abnormalities were also performed.

Results

Progressive MS patients presented higher GM–TSC values (48.8 ± 3.1 mmol/l wet tissue vol, p < 0.001) and T₂lesions-TSC values (50.9 ± 2.2 mmol/l wet tissue vol, p = 0.01) compared to GM and WM of controls. Statistical mapping analysis showed TSC increases in PPMS patients confined to motor and somatosensory cortices, prefrontal cortices, pons and cerebellum. In SPMS, TSC increases were associated with areas involving: primary motor, premotor and somatosensory cortices; prefrontal, cingulate and visual cortices; the corpus callosum, thalami, brainstem and cerebellum. Anterior prefrontal and premotor cortices TSC were correlated with disability.

Conclusion

Sodium accumulation is present in progressive MS patients, more restricted to the motor system in PPMS and more widespread in SPMS. Local brain sodium accumulation appears as a promising marker to monitor patients with progressive MS.     

Real-time volume rendering of MRCP: clinical applications

MR-cholangiopancreatography (Signa Contour 0.5T; GE/Medical Systems, Milwaukee, WI) data sets of 156 patients, obtained with a 2D T2-weighted FSE sequence, in the coronal plane, were volume rendered (Advantage Windows 3.1; GEMS) independently by two radiologists, that were asked to define the range of signal intensitics in which the signal of the pancreaticobiliary system was included and to rank the quality of native images and volume renderings. Patients had biliary stones (n=47), inflammatory ampullary stenoses (n=18), pancreaic tumors (n=12), surgical bilio-enteric anastomoses (n=19), ampullary carcinomas (n=2), pancreatic duct stone (n=1), cholangiocarcinoma (n=3) and normal pancreaticobiliary tree (n=54). Good quality volume renderings of the bile ducts were obtained for at least a maximum diameter of 1.5 mm. The quality rank agreement between volume rendering and native images was excellent (k=0.94). The correlation between the observers for the setting the signal intensity range was excellent and statistically significant (p<0.001). The correlation between the observers for the time of volume rendering was not statistically significant. Bilary stones could be displayed in 32/47 (68%) cases. The pancreatic duct stones was displayed as well. Inflammatory ampullary stenoses were detected in all cases (100%). In case of pancreatic tumors, cholangiocarcinomas and ampullary carcinomas volume rendering allowed to identify the site of stenosis. In surgical bilio-enteric anastomoses volume rendering was helpful to display the residual bilary tract, the site of anastomosis and the enteric tract. Volume rendering could be a reliable and efficient tool for the study of the anatomy and pathological changes of the pancreaticobiliary tract. Note: keywords have been selected from the Index to imaging literature (January 1999), of the RSNA (Supplement to Radiology).     

Investigation of blood-brain barrier permeability to magnetite-dextran nanoparticles (MD3) after osmotic disruption in rats

The permeability of experimentally disrupted blood-brain barrier (BBB) to superparamagnetic nanoparticles (MD3) was studied in rats. BBB opening was induced by intracarotid injection of mannitol. One hundred eighty rats were used for the study. Rats were examined at two time points, 30 minutes and 12 hours after intracarotid mannitol injection. Different preparations intravenously injected 30 minutes before rat sacrifice were used for characterization of BBB disruption. BBB integrity was determined with^99mTc-diethylenetriamine pentaacetic acid (DTPA) and^99mTc-albumin. Iron oxide-glucose particles (12-nm mean diameter),^99mTc-labeled lecithin-cholesterol liposomes of three different sizes (50, 100, and 200 nm), and polyethylene glycol (PEG)-coated^99mTc liposomes (50 nm) were used for investigations of the dependence of BBB permeability on particle system size or surface. Magnetite-dextran nanoparticles (MD3) were evaluated as superparamagnetic contrast agent to monitor with magnetic resonance imaging (MRI) the BBB breakdown.In vitro T₁ and T₂ relaxation times of the brain tissue were measured at 40 MHz and 37°C, and T₂-weighted MR images were acquired at 0.5 T. After intracarotid mannitol infusion, as expected, the BBB breakdown was immediate and temporary as judged by soluble molecule diffusion. MD3 nanoparticles crossed the BBB 12 hours after intravenous mannitol injection, at a time when brain permeability for molecules or small particles returns to normal. Magnetite crystals were found in cytoplasmic vesicles of glial cells. On MRI, signal intensity decreased after injection of MD3, even 12 hours after mannitol injection. This particularity could be useful in the study of focal pathological lesions accompanied by BBB permeability modifications. In such conditions, superparamagnetic particle contrast agents could be caught by the BBB, allowing the observation of impaired BBB areas without detectable cellular lesions. V. Rousseau was supported by a grant from the city of Angers.     

Comparison of breath-hold 2D phase-contrast with non breath-hold cine phase-contrast MRA in the assessment of azygos venous blood flow in portal hypertension

Azygos venous blood flow as an index of blood flow through the gastroesophageal collaterals and varices is of value in the prediction of gastrointestinal bleeding. Measurement of azygos venous blood flow has been achieved by non breath-hold (NBH) cine phase-contrast magnetic resonance imaging. The objective of this study was to compare the faster breath-hold (BH) phase-contrast technique with the standard (NBH) cine phase-contrast technique in the measurement of azygos blood flow. Thirty-two cirrhotic patients with esophageal varices were examined by magnetic resonance imaging using a BH technique and a NBH cine phase-contrast technique to measure the flow velocity, flow volume and calibre of the azygos vein at the mid-right atrial level. The flow values were obtained on the velocity image of the phase-contrast study. Values obtained from the two methods were evaluated statistically for the strength and significance of correlation by the Pearson test. Measurement by the BH method performed at full-inspiration as well as end-expiration was also obtained in 15 healthy volunteers. The breath-hold phase-contrast method has significant but weak correlation with non BH cine phase-contrast method in the measurement of azygos venous blood flow volume (r=0.55, p<0.01) and flow velocity (r=0.43, p=0.01). However, the calibre of the azygos vein gave a strong correlation in these two methods (0.82). In the subgroup of patients whose azygos blood flow velocity was greater than 7.4 cm/s, the correlation of azygos blood flow volume is strong (r=0.80, p<0.01). The azygos vein calibre remains highly correlated between the BH and NBH method, in both high flow velocity (r=0.73) and low flow velocity (r=0.83) groups. Breath-hold sequence leads to higher values for flow velocity and flow volume in the cirrhotic patients and also the control group. In patients with portal hypertension, BH 2D phase-contrast (PC) magnetic resonance angiography (MRA) could give a comparable estimation of the calibre of the azygos vein as the NBH 2D cine PC MRA but not for azygos flow volume. In patients with high azygos flow velocity, the strong correlation in flow volume between the BH and NBH method suggests that the BH method may be a time-saving alternative to the NBH method.     

Relevance of the skewness index in DTI exploration of multiple sclerosis

Object  To this day, no parameter can really monitor the progression of multiple sclerosis (MS). In this study, an index the skewness (S) derived from parameters calculated in diffusion tensor imaging (DTI) has been tested on MS patients for its ability to monitor the disease course. Materials and methods  Eighteen patients underwent two examinations within 3 months consisting of a clinical evaluation (EDSS) and DTI acquisitions on a 1.5 T imager. Tensor was calculated thanks to“home-made” software. Mean diffusivity (MD) and fractional anisotropy (FA) histograms were described for normal-appearing white matter (NAWM) and gray matter (GM) of patients with S and also with usually indices peak position (pp) and peak height (ph) for the whole group of patients and for two separate groups according to their clinical status (EDSS  ≤  3 and EDSS  > 3 at month 0). Results  Although no significant clinical evolution is observed over 3 months, S in GM showed a significant shift for both MD/FA histograms towards abnormal values for the whole group of patients (p = 0.02/p = 0.04) and for the group with EDSS  ≤  3 (p = 0.04/p = 0.007), while ph and pp do not. Conclusion  S in GM could be an alternative marker to monitor the disease course before the repercussion on the clinical score.     

Monitoring the development of hepatocellular carcinoma in woodchucks using 31P-MRS

The woodchuck is one of the only lab animal models of chronic viral hepatitis infection and the development of hepatocellular carcinoma. Using this model, changes in tissue energetics in the liver due to the development of hepatocellular carcinoma can be monitored by repeated magnetic resonance imaging and localized phosphorus spectroscopy. Age- and sex-matched control (n=5) and chronically infected (n=5) adult woodchucks were imaged four times in a six-month period in a 7-T horizontal-bore magnet. Using a custom-built doubly tunable quadrature volume coil, sagittal and axial FLASH images (128×128, slice thickness = 5 mm, TR/TE=1000/4.1, 8 averages) were acquired to locate the largest portion of the liver with the least amount of signal contamination from surrounding abdominal muscle. Two-dimensional 31P chemical-shift imaging (2D-CSI) was acquired (16×16 data matrix, 24×24×2 cm³, 1024 data points, 16 averages) for all animals. The extent of liver injury was determined using serum gamma glutamyltransferase (GGT). The livers of infected woodchucks showed a significant increase (p=0.01) in phosphomonoesters (PME):β-adenosine triphosphate (NTP). Chronically infected woodchucks had higher levels of serum GGT compared to uninfected woodchucks (p=0.002). An increase in the PME:β-NTP ratio indicates cellular proliferation within the malignant tumor.     

MR imaging of baker cysts—prevalence and relation to internal derangements of the knee

Rationale and objectives: To evaluate the prevalence of popliteal cysts in patients studied with magnetic resonance (MR) imaging. Cyst presence and volume will be related to other internal derangement of the knee.Materials and methods: Three hundred and eighty-two consecutive patients with a MR study of the knee were included. Images were obtained in the three spatial orthogonal planes and evaluated through consensus. Four categories were established for the Baker cyst and synovial fluid (absence, minimum, moderate and massive), and the presence of meniscal, cruciate ligaments and cartilage lesions were recorded. Statistical analysis was carried out with bivariate analysis (χ² of Pearson and Gamma tests).Results: From the 382 patients, 145 had Baker cysts (38.0%). Cyst content was minimum in 99, moderate in 34 and massive in 12. Joint effusion was observed in 269 patients (70.4%), being minimal in 140 patients, moderate in 119 and massive in ten. Meniscal lesions were observed in 195 patients (51%), while 58 patients (15%) had a cruciate ligament lesion. Baker cyst has a statistically significant direct relationship with the presence and quantity of synovial fluid (P=0.002) and with the presence and type of meniscal lesion (P=0.01) but not with cruciate ligaments or cartilage lesions.Conclusions: The prevalence of Baker cysts in MR studies of the knee is high. Its presence and volume are related to the quantity of synovial fluid, and to the presence and severity of meniscal lesions.     

Pathophysiological changes after traumatic brain injury: comparison of two experimental animal models by means of MRI

In an experimental study MRI was used to compare the pathophysiological changes of brain tissue after lateral fluid percussion injury (FPI) versus cold injury (CI) as models of traumatic brain injury (TBI). Two groups of Sprague-Dawley rats (n = 23) were subjected to mild FPI, respectively, CI localized over the right parietal cortex. MRI was performed at different time points including Tlw, T2w and Tlw-CE (Gd-DTPA 0.2 mmol/kg BW) sequences as well as perfusion-weighted imaging with calculation of regional cerebral blood volume (rCBV) and regional cerebral blood flow (rCBF). T2w and Tlw-CE images showed hyperintense areas in the traumatised cortex demonstrating brain edema and blood-brain barrier (BBB)-breakdown increasing up to 12 h. Perfusion-weighted imaging demonstrated a significant decrease of rCBV and rCBF in the ipsilateral cortex of CI animals compared with the contralateral hemisphere. In contrast, rats of the FPI group showed only slight differences in rCBF and rCBV comparing the left and right cortex. The results of our study confirm that both mild FPI and CI produced focal brain edema with concomitant breakdown of the BBB as a model of TBI. Since differences regarding perfusion are much more pronounced in CI our results suggest that, this model more likely seems to reflect pathophysiological changes of brain ischemia, whereas FPI seems to be better suited to model the pathophysiological characteristics of TBI.     

The feasibility of a novel limited field of view spiral cine DENSE sequence to assess myocardial strain in dilated cardiomyopathy

Objective

Develop an accelerated cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance (CMR) sequence to enable clinically feasible myocardial strain evaluation in patients with dilated cardiomyopathy (DCM).

Materials and methods

A spiral cine DENSE sequence was modified by limiting the field of view in two dimensions using in-plane slice-selective pulses in the stimulated echo. This reduced breath hold duration from 20RR to 14RR intervals. Following phantom and pilot studies, the feasibility of the sequence to assess peak radial, circumferential, and longitudinal strain was tested in control subjects (n = 18) and then applied in DCM patients (n = 29).

Results

DENSE acquisition was possible in all participants. Elements of the data were not analysable in 1 control (6%) and 4 DCM r(14%) subjects due to off-resonance or susceptibility artefacts and low signal-to-noise ratio. Peak radial, circumferential, short-axis contour strain and longitudinal strain was reduced in DCM patients (p < 0.001 vs. controls) and strain measurements correlated with left ventricular ejection fraction (with circumferential strain r = − 0.79, p < 0.0001; with vertical long-axis strain r = − 0.76, p < 0.0001). All strain measurements had good inter-observer agreement (ICC > 0.80), except peak radial strain.

Discussion

We demonstrate the feasibility of CMR strain assessment in healthy controls and DCM patients using an accelerated cine DENSE technique. This may facilitate integration of strain assessment into routine CMR studies.

     

1H spectroscopy in stroke

We used proton spectroscopy to compare metabolite levels in infarcted brain tissue with the levels in corresponding normal white matter. In a preliminary study of six patients, the ratios (mean ± standard deviation) were 0.72±0.25 (p=0.04) for choline, 0.41±0.24 (p=0.002) for creatine, and 0.21±0.22 (p<0.001) forN-acetylaspartate.     

Breakdown mechanism of capacitively coupled RF discharges

Measured breakdown characteristics of capacitively coupled RF discharges are compared with numerical simulations performed under different boundary conditions at the electrode. When a pair of glass‐covered aluminum disks are used in the breakdown measurement of N₂ and Ar gases at RF frequency of 13.56 MHz, the peculiar bend in the left branch of the minimum of V‐shaped breakdown curves is not observed, suggesting the absence of secondary electron emission. For the treated boundary condition of the electron density n, the simulation with the zero gradient gives satisfactory agreement with the experimental V‐shaped curves, while the simulation with n = 0 is shown to be effective in the region of small electric fields. The development of RF breakdown is explained based on the simulation for spatiotemporal profiles of n. © 1999 Scripta Technica, Electr Eng Jpn, 130(1): 8–14, 2000     

An analysis of the intracerebral ability to eliminate a nitroxide radical in the rat after administration of idebenone by anin vivo rapid scan electron spin resonance spectrometer

Electron spin resonance (ESR) measurements after intracerebroventricular injection of a nitroxide radical were carried out in rats (n=6) that received oral idebenone for 2 weeks and in control rats (n=5), using anin vivo rapid scan ESR spectrometer. The half-life of nitroxide, which was estimated from the change in the peak height (M=+1) of the ESR signals from the head, was used as a marker for the elimination of the nitroxide radical. The half-life in the rats treated with idebenone was significantly shorter than it was in the controls (p<0.05). This finding indicates that the treatment with idebenone can enhance the intracerebral-eliminating ability of the nitroxide radical.     

GLINT: GlucoCEST in neoplastic tumors at 3 T—clinical results of GlucoCEST in gliomas

Objective

Clinical relevance of dynamic glucose enhanced (DGE) chemical exchange saturation transfer (CEST) imaging has mostly been demonstrated at ultra-high field (UHF) due to low effect size. Results of a cohort study at clinical field strength are shown herein.

Materials and methods

Motion and field inhomogeneity corrected T1ρ‐based DGE (DGE⍴) images were acquired before, during and after a d-glucose injection with 6.3 s temporal resolution to detect accumulation in the brain. Six glioma patients with clear blood–brain barrier (BBB) leakage, two glioma patients with suspected BBB leakage, and three glioma patients without BBB leakage were scanned at 3 T.

Results

In high-grade gliomas with BBB leakage, d-glucose uptake could be detected in the gadolinium (Gd) enhancing region as well as in the tumor necrosis with a maximum increase of ∆DGE⍴ around 0.25%, whereas unaffected white matter did not show any significant DGE⍴ increase. Glioma patients without Gd enhancement showed no detectable DGE⍴ effect within the tumor.

Conclusion

First application of DGE⍴ in a patient cohort shows an association between BBB leakage and DGE signal irrespective of the tumor grade. This indicates that glucoCEST corresponds more to the disruptions of BBB with Gd uptake than to the molecular tumor profile or tumor grading.

     

Neuromyelitis optica does not impact periventricular venous density versus healthy controls: a 7.0 Tesla MRI clinical study

Objective

To quantify the periventricular venous density in neuromyelitis optica spectrum disease (NMOSD) in comparison to that in patients with multiple sclerosis (MS) and healthy control subjects.

Materials and methods

Sixteen patients with NMOSD, 16 patients with MS and 16 healthy control subjects underwent 7.0-Tesla (7T) MRI. The imaging protocol included T₂*-weighted (T₂*w) fast low angle-shot (FLASH) and fluid-attenuated inversion recovery (FLAIR) sequences. The periventricular venous area (PVA) was manually determined by a blinded investigator in order to estimate the periventricular venous density in a region of interest-based approach.

Results

No significant differences in periventricular venous density indicated by PVA were detectable in NMOSD versus healthy controls (p = 0.226). In contrast, PVA was significantly reduced in MS patients compared to healthy controls (p = 0.013).

Conclusion

Unlike patients with MS, those suffering from NMOSD did not show reduced venous visibility. This finding may underscore primary and secondary pathophysiological differences between these two distinct diseases of the central nervous system.

     

Brain T2 relaxation times correlate with regional cerebral blood volume

We previously reported cerebellar and putaminal transverse relaxation time (T2) differences in children with ADHD and in adults with childhood trauma. As brain T2 can be altered by deoxyhemoglobin concentration ([dHb]) and because [dHb] is proportional to regional cerebral blood volume (rCBV), at steady state we attributed those differences to rCBV changes. Studies in other species have established a correlation between T2 and rCBV; however this has yet to be demonstrated in human brain. Echo planar imaging (EPI) T2 relaxometry and dynamic susceptibility-contrast (DSC) MRI were used to measure T2 and rCBV in 11 healthy adults. Significant T2-rCBV correlations were observed in both cerebellar vermis and putamen (r=0.759,p=0.007;r=0.782,p=0.004, respectively). These correlations predict 9±3% and 10±3% rCBV changes, respectively, for each 1-msec change in T2. Consequently, brain T2 measurements may be useful for estimating steady-state rCBV.     

Untersuchung der Sperrfähigkeit hochsperrender p+ n-Strukturen mit mesa-förmiger und inverser Randstufe

Übersicht Es werden die Ergebnisse von Sperrspannungsberechnungen an zwei unterschiedlichenp ⁺ n-Strukturen vorgestellt. Die Resultate werden durch Lösung der zweidimensionalen Poisson-Gleichung mit der Methode der finiten Differenzen erzielt. In einer umfangreichen Parameterstudie werden Strukturen mit einer mesa-artigen Randkontur und Strukturen mit inverser Randstufe untersucht. Besondere Aufmerksamkeit gilt dem Einfluß von positiven Oberflächenladungen auf die Sperrfähigkeit. Daneben werden auch verschiedene geometrische Parameter studiert, deren Einfluß für die Anwendung der genannten Strukturen in Thyristoren bedeutsam sein kann.

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Investigation of the blocking capability of high-voltage p⁺n-devices with a mesa-like contour and an inverse mesa contour

Contents The results of breakdown voltage calculations of two differentp ⁺ ndevices are shown. The calculations are based on the numerical solution of Poisson's equation. Devices with a mesa-like edgecontour and devices with an inverse mesa contour are investigated by an extensive variation of parameters. Special attention is given to the influence of surface charge on the blocking behaviour. Moreover several geometrical parameters are examined, which are important for the fabrication of thyristors.

     

(n +p)-node realizability of Y-matrices of (n + 1)-node resistance n-port networks

Sufficient conditions are established for the (n +p)-node, p>2, realizability of Y-matrices of (n + 1)-node resistance n-port networks. It is shown that these conditions are a generalization of the previous known results for p = 2 and p =n.     

Use of spin-traps during warm ischemia-reperfusion in rat liver: comparative effect on energetic metabolism studied using31P nuclear magnetic resonance

Detection of free radicals by electron spin resonance (ESR) proves the involvement of reactive oxygen species (ROS) in reperfused organ injuries. Spin-traps are known to ameliorate hemodynamic parameters in an isolated postischemic heart. The effects of 5 mmol/L DMPO (5,5-dimethyl-1-pyrroline-N-oxide) or DEPMPO (5-(diethylphosphoryl)-5-methyl-1-pyrrolineN-oxide) on intracellular pH (pH_in) and ATP level were evaluated by³¹P nuclear magnetic resonance on isolated rat liver submitted to 1 hour of warm ischemia and reperfusion. At the end of the reperfusion period, during which pH_in recovered to its initial value (7.16±0.03) in all groups, the ATP recovery level (expressed in percentage of initial value) was similar in controls and DEPMPO (60%±5%,n=6 and 54%±4%,n=6, respectively), but only 37%±1% in DMPO-treated livers (n=6) (p<0.05 versus controls andp<0.05 versus DEPMPO). Oxidative phosphorylation was not affected by an addition of nitrones on isolated mitochondria extracted from livers not submitted to ischemia-reperfusion. In contrast, mitochondria extracted at the end of the ischemia-reperfusion showed an impairment in the phosphorylation parameters, particularly in the presence of DMPO. Mass spectrum of ischemic liver perchloric acid extracts evidenced probable catabolites in treated groups. The differences in the effect of the two nitrones on energetic metabolism may be explained by the production of deleterious catabolites by DMPO as compared to DEPMPO. Even though a specific radical scavenging effect could be operative in the liver, our results indicate that catabolic effects were predominant. The absence of deleterious effects of DEPMPO in contrast to DMPO on the liver energetic metabolism was evidenced, allowing the use of DEPMPO for ESR detection.     

Distribution of gadomelitol in a human breast tumor model in mice

The study evaluates the tumor distribution of the rapid clearance blood pool agent (RCBPA) gadomelitol, in a breast tumor model. Different techniques were used : (1) tissue gadolinium concentrations measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES), (2) whole body quantitative autoradiography using radiolabeled [¹⁵³Gd] gadomelitol and (3) dynamic contrast-enhanced MRI with compartmental analysis. An accumulation of gadomelitol in tumors compared to muscle was observed 30 min and 3 h post injection (p.i.). Thirty minutes p.i., the gadomelitol tumor distribution evaluated by autoradiography showed a marked difference between the rim and the center, whereas both areas showed comparable concentrations after 3 h. Using dynamic contrast-enhanced MRI, three phases could be observed during the 1 hour observation period: (1) rapid tumor uptake within the first few minutes post-injection (2) a progressive increase in tumor signal enhancement over 10 min and (3) a steady-state phase. Average +/− SD (n=5) transendothelial permeability K^PS and the fractional blood volume fBV were 12.2±1.6 μl/min⁻¹/g and 5.4±0.2% respectively. Due to its slow extravasation and high tumor residence time, gadomelitol may potentially be useful to improve characterization between benign versus malignant tumors using dynamic MRI.     

MRI characterisation of a novel rat model of focal astrocyte loss

Blood-brain barrier (BBB) integrity is lost in several neurological conditions in which astrocytes are damaged. We studied 3-chloropropanediol-induced focal lesions, a toxicant that induces early astrocytic (but not neuronal) death followed by BBB leakage. T2-weighted images illustrate regional selectivity of the lesions, affected areas including the inferior colliculi and red nuclei. Gd-DTPA intensity quantified the degree of vascular leakage in the lesioned areas. MRI intensity in lesioned areas peaked at 2 days, correlating with BBB breakdown, and diminished thereafter, returning to pre-injection levels by 30 days in parallel with the return of astrocytes. T2 measurements were unchanged at 6 h, a time when astrocyte swelling is marked but the vasculature is intact, but increased at 2 days, consistent with cellular damage and BBB leakage. Gd-DTPA enhancement was also greatest at 2 days then decreased over the next 28 days, indicating a tracer-size-dependent rate of BBB repair. A simple model based on experimentally acquired data indicated that the vascular breakdown was the result of leakage of only a small percentage of blood vessels in the affected areas. Loss of astrocytes contributes to barrier loss, and restoration of astrocytes is needed for full barrier recovery.