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Diffusion-weighted imaging of fungal cerebral infection.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) is useful in diagnosing bacterial brain abscesses, but DWI features of fungal brain abscesses have not been characterized. Because fungal abscesses are not purulent, we hypothesized that their DWI characteristics are distinct from those of bacterial abscesses. METHODS: We reviewed clinical, neuropathologic and neuroimaging findings of patients with fungal brain infections due to Aspergillus (n = 6), Rhizopus (n = 1), or Scedosporium (n = 1) species. DWI and apparent diffusion coefficient (ADC) maps were obtained before definitive diagnosis and antifungal therapy. ADC ratios (lesion/contralateral white matter) were calculated. RESULTS: Two patients had a rapidly progressive, fatal course, with cerebritis and acute inflammation; fungal organisms were largely restricted to vessels. Lesions were predominantly nonenhancing and had heterogeneous foci of restricted diffusion. Six patients with subacute neurologic presentations had acute or chronic inflammation, capsule formation, focal necrosis, and fungal organisms disseminated throughout the lesion. Their abscesses were ring enhancing. In five, lesions had restricted diffusion in the central nonenhancing portions. The sixth patient had a lesion with a peripheral rim of restricted diffusion but elevated central diffusion; histopathology showed early abscess formation. Mean ADC for all lesions was 0.33 +/- 0.06 x 10(-3) mm(2)/s, with an average ADC ratio of 0.43. CONCLUSION: Fungal cerebral abscesses may have central restricted diffusion similar to that of bacterial abscesses but with histologic features of acute or chronic inflammation and necrosis rather than suppuration. Altered water diffusion in these lesions likely reflects highly proteinaceous fluid and cellular infiltration.

Adult↗

Diffusion tensor tractography of the limbic system.

BACKGROUND AND PURPOSE: The limbic system, relevant to memory and emotion, is an interesting subject of study in healthy and diseased individuals. It consists of a network of gray matter structures interconnected by white matter fibers. Although gray matter components of this system have been studied by using MR imaging, the connecting fibers have not been analyzed to the same degree. Cerebrospinal fluid (CSF) signal intensity contamination of the fornix and cingulum, the 2 major white matter tracts of the limbic system, can alter diffusion-tensor imaging (DTI) measurements and affect tractography. We investigated the effect of CSF signal intensity suppression on fiber tracking of the limbic connections and characterized the diffusion properties of these structures in healthy volunteers. METHODS: Nine healthy individuals were scanned with standard and CSF-suppressed DTI. Tractography of the fornix and cingulum was performed for both acquisition methods. We report mean diffusivity and fractional anisotropy measurements of the crus, body, and columns of the fornix, and descending, superior, and anterior portions of the cingulum. RESULTS: Diffusion measurements were improved and tractography was facilitated by using CSF-suppressed DTI. In particular, tract volume increased, whereas decreases of the mean diffusivity and increases of diffusion anisotropy more accurately represented the underlying tissue by minimizing deleterious partial volume averaging from CSF. This was particularly true for the fornix because it is in closest contact to CSF. Diffusion measurements throughout the limbic connections were consistent in healthy volunteers. CONCLUSION: We recommend the use of CSF suppression when performing diffusion-tensor tractography of the limbic system.

Adult↗

MR diffusion imaging of cerebral infarction in humans.

PURPOSE: MR diffusion imaging was performed to investigate changes in water diffusion in patients with cerebral infarction. METHODS: Diffusion maps of the apparent diffusion coefficient (ADC) were created to show local water mobility in the brain tissue in 15 patients. These ADC maps were compared with conventional T2-weighted images. RESULTS: Distinct subregions with different water diffusions were detected, even when the infarcted area appeared homogeneous on a T2-weighted image. The results also show that stroke lesions of the same age can have very different water diffusions. A trend towards an increasing diffusion coefficient in a lesion during the first several days following an acute event was observed in a group of patients imaged at multiple timepoints. CONCLUSION: The measurement of diffusion coefficients in vivo now offers an opportunity for greater understanding of the biophysical changes that occur during the evolution of infarction in humans.

Adult↗

Diffusion of water in biological tissues.

A method is presented for obtaining simple approximate solutions for the problem of self-diffusion in an ordered array of obstacles. Our results are compared with some previous exact and approximate solutions, and we find that our method agrees well with the exact results over a large range of the volume fraction of the obstructions. It is shown that there is an important distinction between measurements of the diffusion coefficient by the capillary flow method and the spin-echo method. The modifications for the spin-echo case are given and applied to recent measurements on the anisotropy of the self-diffusion of water in striated muscle and to measurements on cysts of the brine shrimp. The analysis shows that very large volume fractions of obstructive barriers are required in order to account for the reduction in the diffusion coefficient in biological systems. Thus this model analysis leads to the supposition that a substantial fraction (20-40%) of the cell water is hydration water, or that the diffusion coefficient of the cytoplasmic water is reduced substantially from the free water value. In either case, the conclusion that a substantial fraction of cell water has diffusive properties that are altered by the macromolecules of the cytoplasm seems inescapable. In the case of NMR methodology, the measuring times are such that the values for diffusion are often influenced by the presence of macromolecular structures (obstructions) within the cells. This suggests that obstructions make a significant contribution to the value of the NMR diffusion coefficient and that NMR may have practical value for the evaluation of obstruction effects.

Animals↗

Glucose diffusivity in multicellular tumor spheroids.

In order to understand the role of glucose limitations in controlling multicellular tumor spheroid growth, knowledge of the glucose diffusion coefficient is essential. The effective diffusivity of glucose in spheroids of rodent and human tumor cell lines has been determined by measuring the efflux of tritium labeled L-glucose from spheroids with time. When the rapid and irreversible binding of L-glucose in spheroids is properly taken into account, measurements of the efflux of this diffusion tracer from spheroids into label-free medium can be correlated to the diffusion equation in order to obtain the effective glucose diffusivity in spheroids. Such measurements have been made in EMT6/Ro mouse mammary tumor spheroids as well as in spheroids derived from human colon carcinoma cells (HT29, CO112, and WiDr) and from human squamous carcinoma cells (CaSki and A431). EMT6/Ro spheroids have a glucose diffusivity of 1.1 x 10(-6) cm2/s, while glucose diffusion coefficients in the human cell spheroids studied vary from 5.5 x 10(-7) cm2/s to 2.3 x 10(-7) cm2/s. These values are low enough to suggest that significant gradients in glucose concentration may exist in spheroids and tumors. It is thus believed that these glucose diffusivities, as well as their variation with cell line, may have important implications for the role played by glucose in the growth and cellular heterogeneity of spheroids and tumors.

Algorithms↗

Estimation of gas-phase diffusivities in hyperbaric environments.

Diffusion of a particular gas in a mixture of three or more gases depends on diffusion characteristics and concentrations of the other gases and also on environmental pressure. 1) Estimates of gas-phase diffusivities in hyperbaric environments can be calculated from binary coefficients by the Wilke equation. Sample calculations show that addition of carbon dioxide and water to inspired gas has very little effect on diffusivity of oxygen but that neglect of lesser components of a mixture, such as the nitrogen in "trimix" or the helium in crude neon, would lead to errors of 10% to 20%. 2) It is not possible to match a compressed air environment with a helium-oxygen or a helium-oxygen-nitrogen environment for both density and diffusivity. Diffusivities of oxygen and carbon dioxide in a helium mixture can be less than half the values in compressed air having the same density. In a plot of diffusivity vs. gas density, most useful mixtures are included in a hyperbolic-shaped band; diffusivity falls to below 25% of the room air value when density is 5 times normal.

Atmospheric Pressure↗

Clinical experience with diffusion-weighted MR in patients with acute stroke.

PURPOSE: Our purpose was to evaluate the clinical efficacy, sensitivity, and specificity of echo-planar diffusion-weighted MR imaging in patients with acute infarction. METHODS: We retrospectively analyzed 194 cases of acute ischemic stroke diagnosed clinically within 24 hours of onset and studied with echo-planar diffusion-weighted MR imaging. Examinations were considered to be positive for infarction when an increase in signal was noted on images acquired at a high b value but absent on images with a low b value. A final clinical diagnosis of acute stroke was used as the standard of reference. A subset of 48 patients scanned within 6 hours was also analyzed. RESULTS: Diffusion-weighted MR imaging studies were positive in 133 of 151 cases of infarction (88% sensitivity) and negative in 41 of 43 cases with no infarction (95% specificity). Two cases identified as positive on diffusion-weighted images had nonischemic diagnoses (1.5% false-positive rate). Diffusion-weighted imaging had a positive predictive value of 98.5% and a negative predictive value of 69.5%. Use of T2-weighted sequences as well as diffusion-weighted imaging produced no false-positive findings. Of the negative scans, 69.5% corresponded to transient ischemic attacks or infarcts (mostly small brain stem infarcts). When only cases scanned within 6 hours of onset were considered, the sensitivity rose to 94% and the specificity to 100%. CONCLUSION: Despite bias due to dependence between diffusion-weighted imaging and the final diagnosis, this analysis suggests high sensitivity and specificity for echo-planar diffusion-weighted imaging in the diagnosis of acute cerebral infarction, although negative scans did not rule out an ischemic pathogenesis.

Acute Disease↗

Abnormal diffusion-weighted magnetic resonance images in Creutzfeldt-Jakob disease.

BACKGROUND: Traditional imaging methods, including computed tomography, routine magnetic resonance imaging (MRI), and magnetic resonance spectroscopy, have not been particularly useful in the diagnosis of Creutzfeldt-Jakob disease (CJD). Although abnormalities can be seen using these methods, the findings are evident only late in the disease or lack specificity or sensitivity. OBJECTIVE: To describe abnormalities on diffusion-weighted MRIs in 4 patients with proven CJD. METHODS: Diffusion-weighted MRIs were obtained on 4 patients with CJD as part of a routine MRI brain examination. RESULTS: In all 4 patients, diffusion-weighted MRIs of the brain demonstrated bilateral hyperintensity in the basal ganglia. In 1 patient, the most conspicuous abnormality seen in diffusion-weighted images was in the thalamus. Two patients also demonstrated hyperintensity in the cerebral cortex on diffusion-weighted images. Only 2 of 4 patients demonstrated clear abnormalities on routine (non-diffusion-weighted) MRIs. Diffusion abnormalities were visible in 1 patient within 1 month of symptom onset. The findings were most conspicuous and extensive in the patient with the longest duration of symptoms (7 months). CONCLUSIONS: Diffusion-weighted MRI might provide a noninvasive method of identifying patients with CJD. However, further investigations must be performed to determine the specificity of these findings for CJD.

Basal Ganglia↗

Diffusion-weighted magnetic resonance imaging in nonconvulsive status epilepticus.

BACKGROUND: In human and experimental models, diffusion-weighted magnetic resonance imaging (DWI) findings in status epilepticus (SE) have been reported to show that apparent diffusion coefficients are reduced during the initial phase and normalized or increased in the later phase of prolonged SE. This effect is caused by cytotoxic edema induced by excitotoxicity. In humans, only focal DWI abnormalities have been reported in partial SE. OBJECTIVES: To report and discuss the DWI findings suggesting diffuse neuronal injury in a patient with nonconvulsive SE. DESIGN AND METHODS: A 56-year-old man was admitted because of changing levels of consciousness over 3 days. On admission he was comatose. He had nystagmoid eye movement, forced eye blinking, and oroalimentary automatism. The results of a search for possible infectious and metabolic etiologies were negative, and electroencephalographic findings showed continuous, semirhythmic, bifrontal sharp waves of 2 Hz. Phenytoin and midazolam hydrochloride were infused to alleviate the seizure activities. He underwent DWI initially (3 days after the onset of seizure) and at the 5-month follow-up. SETTING: The neurology department of a tertiary referral center. RESULTS: During SE, DWI findings showed marked, diffuse gyriform cortical hyperintensity throughout the brain. The apparent diffusion coefficient decreased in the corresponding areas, especially in the occipital lobes. Findings from T2-weighted magnetic resonance imaging showed the intense cortical hyperintensity with gyral swelling and no involvement of brainstem, basal ganglia, thalamus, and white matter. The follow-up DWI findings showed marked atrophy and hypointensity in the corresponding regions. The apparent diffusion coefficient increased in the corresponding regions. CONCLUSIONS: Diffusion-weighted imaging in our patient indicated that the magnetic resonance imaging abnormalities of the affected cortex were due to cytotoxic edema caused by neuronal excitotoxicity during prolonged SE. Diffusion-weighted imaging can be used in the localization of seizure focus for predicting the prognosis of the affected tissue and for researching the basic pathophysiology of SE.

Brain↗

Predictors of diffuse-type in-stent restenosis after coronary stent implantation.

Diffuse-type in-stent restenosis (ISR) is associated with higher rate of restenosis after balloon angioplasty, requiring new therapeutic modalities; therefore, it is clinically important to identify the determinants of diffuse-type ISR. We evaluate the clinical and angiographic variables to predict diffuse-type ISR after coronary stent placement. Two hundred and ten ISR lesions in 196 patients (diffuse ISR, 114 lesions; focal ISR, 96 lesions) were reviewed in this study. Clinical, procedural and quantitative coronary angiographic parameters were analyzed. Diffuse-type ISR was defined as a > or = 50% lumen narrowing and > or = 10-mm length. Univariate analysis revealed that initial lesion length, smaller vessel size, diabetes, multivessel disease, multiple stents, and long stent were significantly associated with diffuse-type ISR. However, diabetes was the only independent predictor of diffuse-type ISR by stepwise multiple regression analysis (OR, 3.3; 95% CI, 1.4-7.4, P = 0.001). Diabetes was associated with diffuse-type ISR after coronary stent placement. It may reflect enhanced rate of neointimal hyperplasia within the stent in diabetic patients.

Angioplasty, Balloon, Coronary↗

Diffusion- and perfusion-weighted MRI response to thrombolysis in stroke.

Diffusion- and perfusion-weighted magnetic resonance imaging provides important pathophysiological information in acute brain ischemia. We performed a prospective study in 19 sub-6-hour stroke patients using serial diffusion- and perfusion-weighted imaging before intravenous thrombolysis, with repeat studies, both subacutely and at outcome. For comparison of ischemic lesion evolution and clinical outcome, we used a historical control group of 21 sub-6-hour ischemic stroke patients studied serially with diffusion- and perfusion-weighted imaging. The two groups were well matched for the baseline National Institutes of Health Stroke Scale and magnetic resonance parameters. Perfusion-weighted imaging-diffusion-weighted imaging mismatch was present in 16 of 19 patients treated with tissue plasminogen activator, and 16 of 21 controls. Perfusion-weighted imaging-diffusion-weighted imaging mismatch patients treated with tissue plaminogen activator had higher recanalization rates and enhanced reperfusion at day 3 (81% vs 47% in controls), and a greater proportion of severely hypoperfused acute mismatch tissue not progressing to infarction (82% vs -25% in controls). Despite similar baseline diffusion-weighted imaging lesions, infarct expansion was less in the recombinant tissue plaminogen activator group (14cm(3) vs 56cm(3) in controls). The positive effect of thrombolysis on lesion growth in mismatch patients translated into a greater improvement in baseline to outcome National Institutes of Health Stroke Scale in the group treated with recombinant tissue plaminogen activator, and a significantly larger proportion of patients treated with recombinant tissue plaminogen activator having a clinically meaningful improvement in National Institutes of Health Stroke Scale of > or = 7 points. The natural evolution of acute perfusion-weighted imaging-diffusion-weighted imaging mismatch tissue may be altered by thrombolysis, with improved stroke outcome. This has implications for the use of diffusion- and perfusion-weighted imaging in selecting and monitoring patients for thrombolytic therapy.

Acute Disease↗

In vivo NMR diffusion spectroscopy: 31P application to phosphorus metabolites in muscle.

Apparent diffusion coefficients (Da) of individual metabolites can be studied in vivo by diffusion NMR spectroscopy using an echo sequence sensitized to molecular motion. The methods are based on the echo attenuation due to phase dispersion resulting from incoherent displacement during the diffusion time. As the displacement of metabolites by diffusion in vivo can be affected by compartment size, temperature, adsorption processes, etc., the presented methods are potentially useful in studying such phenomena in vivo. Here, the methods are applied to phosphocreatine in the rat quadriceps muscle. It is demonstrated that the displacement of phosphocreatine resembles free diffusion for short diffusion times but becomes limited as a result of boundaries due to compartmentation for longer diffusion times. The limit of the displacement indicates an apparent average size of 44 microns of the compartment in the direction of the diffusion gradient. As the gradient was applied approximately parallel (angle less than 25 degrees) to the muscle fiber, this result indicates that phosphocreatine moves freely in the cytosol but is limited by the boundaries of the muscle cells. Error analyses are performed with regard to motion artifacts and gradient performance. The methods were tested extensively for distilled water and free metabolites.

Animals↗

Effects of diffusion anisotropy on lesion delineation in a rat model of cerebral ischemia.

The effects of white and gray matter diffusion anisotropy on ischemic lesion delineation have been studied in the rat model of middle cerebral artery occlusion. Apparent diffusion coefficient (ADC) maps obtained by conventional pulsed gradient spin echo diffusion-weighted imaging (PGSE-DWI) were compared with maps of the trace of the diffusion tensor in both normal and occluded animals. Diffusion tensor trace maps were derived from the average of the ADC maps from three separate experiments with diffusion weighting along three orthogonal axes, and also from a single-scan method. A marked degree of diffusion anisotropy was observed in both cortical gray matter and white matter from ADC maps of the control animals. In the occluded animals, the systematic effects of anisotropy on ADC and lesion area influenced the delineation of the ischemic territory in the PGSE-DWI ADC maps. However, the two trace methods eliminated these effects and gave consistent ischemic lesion depiction, despite the use of differing diffusion times in the two measurements.

Animals↗

Diffusion approximation of the stochastic process of microtubule assembly.

Microtubules are protein polymers that guide intracellular motility. Stochastic switching of a microtubule between states of elongation, shortening, and pause is described in detail by the dynamic instability (DI) model. Recently we have described the dynamics of microtubules phenomenologically as generalized diffusion of their ends. Genesis of the diffusion dynamics and accuracy of diffusion model are studied in this work. It is shown that wandering of the end of a microtubule undergoing DI asymptotically approaches the Wiener diffusion process. Accuracy of the diffusion approximation is evaluated by comparing its predictions with results of simulation of DI. Stationary distributions of microtubule length and life-time that are predicted by both models differ qualitatively between two cell types considered. However, predictions of the diffusion model are in each case practically identical to predictions of the DI model being also consistent with experimental data. The peculiar stochastic process of microtubule assembly thus converges at cell scale to a kind of widespread-in-nature diffusion process. This result is considered an example of qualitative change in dynamical properties in transition from the molecular to cellular level of biological organization. Additionally, it suggests employment of diffusion process theory in studying functions of microtubules in the cell.

Animals↗

Diffusion-weighted imaging of the spine using radial k-space trajectories.

INTRODUCTION: Diffusion-weighted MR imaging (DWI) of the spine requires robust imaging methods, that are insensitive to susceptibility effects caused by the transition from bone to soft tissue and motion artifacts due to breathing, swallowing, and cardiac motion. The purpose of this study was to develop a robust imaging method suitable for DWI of the spine. METHODS AND SUBJECTS: A radial k-space spin echo sequence has been implemented, which is self-navigating because each acquisition line passes through the origin of k-space. Influence of cardiac motion and associated flow of cerebrospinal fluid is minimized by cardiac gating with a finger photoplethysmograph. The sequence has been tested on a 1.5T system. Diffusion-weighted images of six normal volunteers were acquired in the sagittal plane with 4 b values between 50 and 500 s mm(-2). Because of the symmetries of the cord, diffusion measurements in the head-foot (HF) or left-right (LR) directions were sufficient to measure the dominant effects of anisotropy. RESULTS: The apparent diffusion coefficients (ADCs) measured, respectively, in the LR and HF directions were (0.699+/-0.050)x10(-3) and (1.805+/-0.086)x10(-3) mm(2) s(-1) in the spinal cord, (1.588+/-0.082)x10(-3) and (1.528+/-0.052)x10(-3) mm(2) s(-1) in the intervertebral disks, and (0.346+/-0.047)x10(-3) and (0.306+/-0.035)x10(-3) mm(2) s(-1) in the vertebrae of the cervicothoracic spine. CONCLUSION: Diffusion-weighted spin echo sequences with radial trajectories in k-space provide a means of achieving robust, high quality diffusion-weighted imaging and measuring ADCs in the spine. The application of the diffusion-weighting gradients in different directions allows diffusion anisotropy to be measured.

Humans↗

Comparison of vessel wall morphologic appearance at sites of focal and diffuse coronary vasospasm by intravascular ultrasound.

Coronary vasospasm is manifested by either focal or diffuse pattern in clinical settings. To examine the differences in vessel wall morphologic appearance between the sites of focal and diffuse vasospasm, we studied 29 patients with chest pain at rest, during exertion, or both by intravascular ultrasound. By angiography, focal vasospasm with diameter reduction of 90% +/- 3% (mean +/- SD) was provoked by intracoronary ergonovine (0.01 to 0.04 mg) in 15 patients. Diffuse vasospasm with diameter reduction of 79% +/- 5% (NS) was provoked in seven patients, and the remaining seven patients served as the control group. By ultrasonography, a significantly thickened intimal leading edge with sonolucent zone was observed in 55 sites from 22 coronary arteries with either focal or diffuse vasospasms (0.61 +/- 0.32 mm), although these sites were normal or minimally narrowed by angiography. Seven segments from the control group exhibited a thin intimal leading edge with sonolucent zone (0.23 +/- 0.08 mm, p < 0.01). When the thickness of the intimal leading edge with sonolucent zone was compared between the abnormal sites with focal and diffuse vasospasm, this was significantly greater at focal spasm, 1.01 +/- 0.35 mm (n = 15), than that at diffuse spasm, 0.46 +/- 0.13 mm (n = 40, p < 0.01). At the sites with diffuse spasm, some of the lesions lay scattered along the coronary vessels, although the lesions were localized at the sites of focal vasospasm. These results indicate that atherosclerosis is present at sites with both focal and diffuse vasospasm even in the absence of angiographically significant coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

X-irradiation-induced changes in the diffusion parameters of the developing rat brain.

Three diffusion parameters of brain tissue, extracellular space volume fraction (alpha), tortuosity (lambda) and non-specific uptake (kappa') of tetramethylammonium were studied in the somatosensory neocortex and subcortical white matter of the rat during postnatal development (postnatal days 2-21) after X-irradiation at postnatal days 0-1. The diffusion parameters were determined from extracellular concentration-time profiles of tetramethylammonium. The tetramethylammonium concentration was measured in vivo with ion-selective microelectrodes positioned 130-200 microns from an iontophoretic source. X-irradiation with a single dose of 40 Gy resulted in typical early morphological changes in the tissue, namely cell death, DNA fragmentation, extensive neuronal loss, blood-brain barrier damage, activated macrophages, astrogliosis, increase in extracellular fibronectin and concomitant changes in all three diffusion parameters. The changes were observed as early as 48 h post-irradiation (at postnatal days 2-3) and still persisted at postnatal day 21. On the other hand, X-irradiation with a single dose of 20 Gy resulted in relatively light neuronal damage and loss, while blood-brain barrier damage, astrogliosis and changes in diffusion parameters were not significantly different from those found with 40 Gy. It is known that the volume fraction of the extracellular space in the non-irradiated cortex is large in newborn rats and diminishes with age [Lehmenkühler A. et al. (1993) Neuroscience 55, 339-351]. X-irradiation with a single dose of 40 or 20 Gy blocked the normal pattern of volume fraction decrease during postnatal development, and in fact brought about a significant increase. At postnatal days 4-5, alpha increased to 0.49 +/- 0.036 in layer III, 0.51 +/- 0.042 in layer IV, 0.48 +/- 0.02 in layer V, 0.48 +/- 0.028 in layer VI and 0.48 +/- 0.025 in the white matter. The large increase in alpha persisted three weeks after X-irradiation. Tortuosity and non-specific uptake decreased significantly at postnatal days 2-5; at days 8-9 they were not significantly different from those of control animals, while they increased significantly at days 10-21. Less pronounced but significant changes in all three diffusion parameters were also found in areas in the ipsilateral hemisphere adjacent to directly X-irradiated cortex. Compared to the control animals [Lehmenkühler A. et al. (1993) Neuroscience 55, 339-351], a significant decrease of alpha, lambda and kappa' was found in the contralateral hemisphere 48-72 h after X-irradiation. Later, alpha values were not significantly different from those in control animals. The decrease in lambda persisted at postnatal days 4-5. A significant increase in lambda and kappa' was found at postnatal days 18-21. We conclude that X-irradiation of the brain in the early postnatal period, even when it results in only relatively light damage, still produces changes in all three diffusion parameters, particularly a large increase in extracellular space volume fraction in all cortical layers, and in the subcortical white matter. Such changes in extracellular volume fraction of the brain can contribute to impairment of signal transmission, e.g. by diluting ions and neuroactive substances released from cells, and can play an important role in functional deficits, as well as in the impairment of developmental processes. Moreover, the increase in tortuosity (inferred from the decrease in apparent diffusion coefficient) in the X-irradiated cortex, as well as in the contralateral hemisphere, suggests that, even when extracellular volume is large, the diffusion of the substances is substantially hindered.

Animals↗

Diffuse pulmonary infiltrates after bone marrow transplantation: the role of open lung biopsy.

BACKGROUND: Diffuse pulmonary infiltrates is the major complication and cause of mortality after bone marrow transplantation. We analyzed the etiologies and prognostic factors in bone marrow recipients with diffuse pulmonary infiltrates and assessed the role of open lung biopsy in managing this complication. METHODS: Medical records of patients with diffuse pulmonary infiltrates after bone marrow transplantation were reviewed. Possible prognostic factors were analyzed by multivariate logistic regression. RESULTS: Sixty-eight (20%) of 341 bone marrow recipients had diffuse pulmonary infiltrates and 34 died. Thirty-five underwent open lung biopsy, resulting in therapeutic changes in 22 (63%) and clinical improvement in 16 (46%). The leading diagnoses were idiopathic interstitial pneumonitis (40%) and cytomegalovirus pneumonitis (20%). Cytomegalovirus pneumonitis caused radiographically observable interstitial infiltrates exclusively and was frequently associated with hepatitis. Idiopathic interstitial pneumonitis resulted in either diffuse ground-glass opacity or interstitial infiltrates. Three (9%) patients had miliary tuberculosis. Respiratory failure (p < 0.001) and acute graft-versus-host disease (p = 0.016) were the poor prognostic factors. CONCLUSIONS: Among bone marrow recipients, we found diffuse pulmonary infiltrates in 20% and a mortality rate of 50%. Idiopathic interstitial pneumonitis and cytomegalovirus pneumonitis were the most common causes and should be suspected in patients with diffuse interstitial infiltrates. In endemic areas, miliary tuberculosis should be suspected in bone marrow recipients with diffuse reticulonodular lesions. Respiratory failure and acute graft-versus-host disease were poor prognostic factors. By establishing a correct diagnosis, open lung biopsy led to treatment changes in about two-thirds of these patients.

Adolescent↗