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Pre-wallerian degeneration in the neonatal brain following perinatal cerebral hypoxia-ischemia demonstrated with MRI.

AIM: Pre-Wallerian degeneration was studied in term and near-term neonates with hypoxic-ischemic brain injury, and related to neurodevelopmental outcome. SUBJECTS: Thirty-nine surviving patients with hypoxic-ischemic encephalopathy or seizures and MRI-documented brain abnormalities were included. Patients were grouped according to the MRI findings: group 1 (n = 23), ischemic stroke or watershed infarcts; group 2 (n = 8), lesions of the basal ganglia; group 3 (n = 8), predominantly white matter lesions. METHODS: Cranial MRI, including diffusion-weighted MRI, was performed between 1 and 10 days after birth. ADC maps were created, and presence or absence of pre-Wallerian degeneration in the cerebral peduncles was assessed. RESULTS: Of the 15 neonates with pre-Wallerian degeneration, 14 had permanent abnormalities of motor development, whereas 1 had a transient asymmetry. Six neonates with a poor outcome had no pre-Wallerian degeneration, which may be contributed to the timing of the MRI in 2. Eighteen neonates had no pre-Wallerian degeneration and a normal motor development. CONCLUSION: Pre-Wallerian degeneration of the cerebral peduncles in neonates with hypoxia-ischemia is almost invariably associated with a poor motor development. In neonates with abnormalities of the basal ganglia or white matter and a poor outcome, pre-Wallerian degeneration is less common than in neonates with stroke or watershed infarcts and a poor motor outcome.

Diffusion Magnetic Resonance Imaging↗

Test liquids for quantitative MRI measurements of self-diffusion coefficient in vivo.

A range of liquids suitable as quality control test objects for measuring the accuracy of clinical MRI diffusion sequences (both apparent diffusion coefficient and tensor) has been identified and characterized. The self-diffusion coefficients for 15 liquids (3 cyclic alkanes: cyclohexane to cyclooctane, 9 n-alkanes: n-octane to n-hexadecane, and 3 n-alcohols: ethanol to 1-propanol were measured at 15-30 degrees C using an NMR spectrometer. Values at 22 degrees C range from 0.36 to 2.2 10(-9) m(2)s(-1). Typical 95% confidence limits are +/-2%. Temperature coefficients are 1.7-3.2% degrees C. T1 and T2 values at 1.5 T and proton density are given. n-tridecane has a diffusion coefficient close to that of normal white matter. The longer n-alkanes may be useful T2 standards. Measurements from a spin-echo MRI sequence agreed to within 2%.

Alcohols↗

Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols.

We describe a standard set of quantity names and symbols related to the estimation of kinetic parameters from dynamic contrast-enhanced T(1)-weighted magnetic resonance imaging data, using diffusable agents such as gadopentetate dimeglumine (Gd-DTPA). These include a) the volume transfer constant K(trans) (min(-1)); b) the volume of extravascular extracellular space (EES) per unit volume of tissue v(e) (0 < v(e) < 1); and c) the flux rate constant between EES and plasma k(ep) (min(-1)). The rate constant is the ratio of the transfer constant to the EES (k(ep) = K(trans)/v(e)). Under flow-limited conditions K(trans) equals the blood plasma flow per unit volume of tissue; under permeability-limited conditions K(trans) equals the permeability surface area product per unit volume of tissue. We relate these quantities to previously published work from our groups; our future publications will refer to these standardized terms, and we propose that these be adopted as international standards.

Contrast Media↗

MRI characterization of diffusion coefficients in a rat spinal cord injury model.

Apparent diffusion coefficients (ADC) were measured in a rat spinal cord weight-drop injury model. After sacrifice, the spinal cords were fixed in situ and excised for MR imaging and ADC measurement. Diffusion is anisotropic in normal gray and white matter. There were significant decreases in ADCs measured along the longitudinal axis of the injured cord and increases in ADCs measured transverse to the cord. Injured segments demonstrated reductions in diffusion anisotropy in the white matter. Diffusion was completely isotropic at the epicenter of the weight-drop injury. Significant decreases in longitudinal ADC and increases in transverse ADC were observed in portions of the cord which appeared normal on conventional spin-echo and calculated T2 images. Thus ADC measurement may complement routine imaging for evaluation of spinal cord injury.

Animals↗

Eclamptic encephalopathy: MRI, including diffusion-weighted images.

Eclampsia is a rare condition peculiar to pregnant and puerperal women. We analyse imaging features in five patients with eclampsia, and determine whether diffusion-weighted imaging (DWI) could differentiate cytotoxic and vasogenic oedema in four of them. All were imaged within 4 days of the onset of symptoms. We found lesions with a prolonged T2 in the brain of all five patients, in the basal ganglia in four, pons in three and posterior cerebral white matter in two. Isotropic DWI revealed variable intensity in these regions. The ADC was decreased in one, and increased in all the others. The lesion with reduced ADC progressed to infarction.

Adult↗

[Diffusion, perfusion and activation functional MRI studies of brain arteriovenous malformations].

The management of Brain Arteriovenous Malformations continues to be challenged by a lack of understanding and control of pathophysiological processes implied in the clinical symptoms. New data from functional MRI with diffusion-weighted, perfusion-weighted and neuronal activation highlight abnormal brain areas near or remote to the AVM nidus. Moreover, these techniques are able to show hemodynamic and neuronal adaptative phenomena involved in brain plasticity. They reflect the instantaneous hemodynamic brain conditions that may help to correlate the clinical symptoms with the anatomical and functional substratum and to influence any invasive therapy.

Brain↗

Midline cerebellar medulloblastoma in a seventy-one-year-old patient.

BACKGROUND: Medulloblastoma is the most common malignant central nervous system tumour in children but, in contrast, quite rare in adults. Hemispheric, rather than midline, cerebellar medulloblastomas are more common in older children and adults. We present the unusual case of a 71-year-old man who presented with a fourth ventricular mass that proved to be a medulloblastoma. METHODS: A 71-year-old man presented with progressive balance problems, slurred speech and double vision. A CT scan of the brain revealed a hyperattenuating, partially calcified, avidly enhancing mass within the fourth ventricle. Diffusion weighted MRI showed restricted diffusion within the mass. The patient underwent a midline suboccipital craniotomy and a subtotal resection was achieved. RESULTS: Histological examination showed a densely cellular neoplasm composed of small cells with a tendency towards neuroblastic rosette formation. Most cells were strongly positive for neuron-specific enolase and synaptophysin. Ultrastructurally, tumour cells showed evidence of neuronal differentiation. These findings were consistent with a classical medulloblastoma. CONCLUSION: Adult medulloblastoma should be considered in the differential diagnosis of a partially calcified hyperattenuating mass within the fourth ventricle.

Aged↗

Rapid breakdown of microvascular barriers and subsequent hemorrhagic transformation after delayed recombinant tissue plasminogen activator treatment in a rat embolic stroke model.

BACKGROUND AND PURPOSE: Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) after stroke increases risk of hemorrhagic transformation, particularly in areas with blood-brain barrier leakage. Our aim was to characterize acute effects of rtPA administration on the integrity of microvascular barriers. METHODS: Stroke was induced in spontaneously hypertensive rats by unilateral embolic middle cerebral artery occlusion. Six hours after stroke, rtPA was intravenously administered (n=10). Controls received saline (n=4). Extravasation of the large-diameter contrast agent monocrystalline iron oxide nanocolloid (MION) was assessed with susceptibility contrast-enhanced MRI during rtPA injection. In addition, we performed perfusion MRI and diffusion-weighted MRI. After MRI, 2 hours after rtPA treatment, intracerebral hemorrhage was quantified with a spectrophotometric hemoglobin assay. RESULTS: Late rtPA treatment resulted in increased hemorrhage volume (8.4+/-1.7 versus 2.9+/-0.9 micro L in controls; P<0.05). In MION-injected animals, during rtPA administration, transverse relaxation rate change (DeltaR2*) increased from 12.4+/-6.0 to 31.6+/-19.2 s(-1) (P<0.05) in areas with subsequent hemorrhage. Significant DeltaR2* changes were absent in nonhemorrhagic areas, in animals without injected MION, and in saline-treated animals. Thrombolytic therapy did not improve perfusion in regions with hemorrhagic transformation (cerebral blood flow index was 22.8+/-19.7% [of contralateral] at 0.5 hours before and 22.4+/-18.0% at 1 hour after rtPA administration). CONCLUSIONS: The DeltaR2* changes during rtPA delivery in MION-injected animals indicate extravasation of MION, which reflects increased permeability of the blood-brain barrier. This implies that late rtPA treatment rapidly aggravates early ischemia-induced damage to microvascular barriers, thereby enhancing hemorrhagic transformation.

Animals↗

Characteristics of CADASIL in Korea: a novel cysteine-sparing Notch3 mutation.

OBJECTIVE: To elucidate the phenotype, genotype, and MRI findings of Korean patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and mutation carriers. METHODS: The authors studied 40 members of nine unrelated Korean CADASIL families. After genetic analysis of Notch3, clinical and MRI findings were correlated in 27 mutation carriers. RESULT: Notch3 mutation sites were C174R (one family, n = 3), R133C (one family, n = 3), R587C (one family, n = 1), R544C (two families, n = 5), and R75P (four families, n = 15). The clinical features were typical of CADASIL, but the frequency of migraine in the Korean population appears low. MRI abnormalities were found in 54% of the mutant carriers, the most common being white matter hyperintensities. The prevalence of lacunes and microbleeds increased with patient age. Anterior temporal areas were less often involved in subjects with R75P mutations than in those where mutations occurred in other sites (p = 0.02). Gradient echo imaging identified microbleedings in 33% of mutation carriers (64% of those with abnormal MRI), whereas diffusion-weighted MRI showed abnormal findings in only one patient. Neurologic disability was related to the number of lacunar infarcts and the lesion volume of white matter hyperintensities (p < 0.001) whereas MMSE score was related to the number of lacunar infarcts (p < 0.005). CONCLUSIONS: Although Korean cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) mutation carriers show similar clinical and MRI findings, these abnormalities appear less frequently than in other populations. Relatively frequent microbleedings on gradient echo imaging suggest that treatment should be individualized according to MRI findings. The novel mutation of R75P, not involving a cysteine residue, is related to less frequent involvement of the anterior temporal area, thus broadening the spectrum of CADASIL.

Adult↗

MR-based technology for in vivo detection, characterization, and quantification of pathology of relapsing-remitting multiple sclerosis.

In relapsing-remitting (RR) multiple sclerosis (MS), conventional magnetic resonance (MR) imaging (MRI) has proved to be a valuable tool to assess the lesion burden and activity over time. However, conventional MRI cannot characterize and quantify the tissue damage within and outside such lesions and only can provide some gross measures reflecting the presence of irreversible tissue damage, such as the load of T1 "black holes" and the severity of brain or cord atrophy. Other MR-based techniques, including cell-specific imaging, magnetization transfer (MT) MRI (MT-MRI), diffusion-weighted (DW) MRI (DW-MRI), proton magnetic resonance spectroscopy (1H-MRS), and functional MRI (fMRI), have the potential to overcome this limitation and, consequently, to provide additional information about the nature and the extent of MS tissue damage, which would inevitably remain undetected when only a conventional MRI is obtained. Cell-specific imaging should result in a better definition of the cellular mechanisms associated with MS inflammation. Metrics derived from MT- and DW-MRI can quantify the structural changes occurring within and outside lesions visible on conventional MRI scans. 1H-MRS could add information on the biochemical nature of such changes. fMRI is a promising technique to assess the mechanisms of cortical reorganization, which may limit the consequences of an MS-related injury. The application of these MR techniques to the study of RRMS is likely to provide useful insights into the pathophysiology of this disease and to improve our ability to assess the efficacy of experimental treatments.

Biopsy, Needle↗

Diffusion-weighted magnetic resonance imaging in brain death.

UNLABELLED: BACKGROUND; Traditionally the diagnosis of brain death is established on the basis of a combination of clinical signs and paraclinical methods. Diffusion-weighted MRI is a new method sensitive to cerebral ischemia. Its value in brain death has not been demonstrated until now. CASE DESCRIPTION: A patient was referred to MRI with suspicion of a brain stem stroke. Echo-planar whole-brain, multislice, diffusion-weighted MRI was performed in addition to conventional sequences and MR angiography sequences. In addition to the extensive bilateral hyperintensities observed on T2-weighted images, diffusion-weighted MRI showed diffuse hyperintensities involving both hemispheres as well as a severe drop in the apparent diffusion coefficient in both affected hemispheres. There was also transtentorial herniation with compression of the brain stem as well as absence of flow voids on the T2-weighted images and absence of intracranial vessels on MR angiography. On the basis of the clinical and imaging findings, it was concluded that the patient was in a state of brain death. The patient died the same day. CONCLUSIONS: With the use of new fast techniques such as diffusion-weighted imaging, now MRI can not only display anatomic changes associated with severe brain suffering but can also demonstrate ultrastructural changes secondary to brain death and differentiate them from edematous changes seen on T2-weighted images.

Aged↗

Relationships between diffusion tensor and q-space MRI.

Fundamental relationships between diffusion tensor (DT) and 3D q-space MRI are derived which establish conditions when these two complementary MR methods are equivalent. It is shown that the displacement distribution measured by q-space MRI in both the large displacement (i.e., large r) and the long-wavelength (i.e., small q) limits is the same 3D Gaussian displacement distribution assumed in DT-MRI. In these limiting cases, q-space MR yields a dispersion tensor that is identical to the effective DT, D, measured in DT-MRI. An experiment is then proposed to measure D using q-space methods. These findings establish that the effective DT, measured in DT-MRI, characterizes molecule motions on a coarse length-scale. Finally, the feasibility of and requirements for performing 3D q-space MRI on a clinical scanner are considered.

Diffusion↗

Comparison of diffusion- and T2-weighted MRI for the early detection of cerebral ischemia and reperfusion in rats.

The sensitivity of diffusion-weighted MRI was compared to that of T2-weighted MRI following temporary middle cerebral artery occlusion (MCA-O) for 33 min followed by 4 h of reperfusion in rats. Diffusion-weighted spin-echo images using strong gradients (b value of 1413 s/mm2) demonstrated a significant increase in signal intensity in ischemic regions as early as 14 min after onset of ischemia in comparison to the normal, contralateral hemisphere (p less than 0.05). This hyperintensity returned to baseline levels during reperfusion. T2-weighted images showed no evidence of brain injury during the temporary occlusion. In three rats subjected to permanent MCA-O, diffusion-weighted MRI demonstrated an increased signal intensity on the first image following occlusion and continued to increase during the 4-h observation period. T2-weighted images failed to demonstrate significant injury until approximately 2 h after MCA-O. Signal intensity ratios of ischemic to normal tissues were greater in the diffusion-weighted images than in the T2-weighted MR images at all time points (p less than 0.05). Close anatomical correlation was found between the early and sustained increase in diffusion-weighted MRI signal intensity and localization of infarcts seen on post-mortem histopathology.

Animals↗

MRI characteristics of acute and subacute brainstem and thalamic infarctions: value of T2- and diffusion-weighted sequences.

MRI including diffusion-weighted sequences (DW-MRI) has demonstrated its high sensitivity for acute supratentorial ischemic lesions. In this study we examined the sensitivity of different MRI sequences for the detection of acute brainstem and isolated thalamic infarctions. Diffusion- and T2-weighted MRI of 45 consecutive patients with signs and symptoms of infratentorial and thalamic infarction between 6/1997 and 1/2000 were analysed. The time between the onset of symptoms and the first MRI varied between 2 hours to 7 days with a median of 2 days. MRI repeats were performed in 4 patients in whom the clinical brainstem infarction had not been detected initially. Lesion detectability and size were evaluated for different brainstem and thalamic localizations. An acute brainstem or thalamic infarction as defined by the clinical condition could be identified in all patients by comparison of DW-MRI and T2-weighted images. Pons in farctions were the largest, followed by midbrain and thalamic lesions. Medulla oblongata infarctions were small in comparison. Pons, mid-brain and thalamic infarctions were reliably identified beginning 12 hours after the onset of symptoms. In contrast, detectability of medulla oblongata infarctions varied within the first 24 hours and their overall visibility was worse than that of other brainstem infarctions corresponding to their small size. However, regardless of loca tion, none of the 3 infarctions examined within the first 5 hours after the onset of symptoms could be identified. These lesions were demonstrated in follow-up examinations. In conclusion, pontine, midbrain and thalamic infarctions can reliably be visualized by a combination of DW-MRI and T2-weighted images beginning 12 hours after the ischemic attack. However, sensitivity seems to be lower earlier than 12 hours after ischemia and for medulla oblongata lesions.

Acute Disease↗

Cytoprotection does not preserve brain functionality in rats during the acute post-stroke phase despite evidence of non-infarction provided by MRI.

In animal models of stroke the promise of a therapy is commonly judged from infarct size measurements, assuming that a reduction in infarct size results in reduction of the functional deficits. We have evaluated the validity of the concept that structural integrity translates into functional integrity during the acute post-stroke period (24 h). Unilateral permanent middle cerebral artery occlusion (pMCAO) in Fischer F344 rats leads to infarcts comprising the ipsilateral striatum and cortical structures, including the somatosensory cortex. Infarct volumes were assessed using magnetic resonance imaging (MRI) methods (T(2), diffusion, perfusion MRI). The functional integrity of the somatosensory cortex was assessed by functional MRI (fMRI) measuring changes in local cerebral blood volume, and by assessing the forelimb grip strength and the beam-walking performance of the animals. Treatment with the calcium antagonist isradipine (2.5 mg/kg injected s.c. immediately after pMCAO) reduced the total infarct size by more than 40% compared to vehicle-injected controls. In particular, the ipsilateral somatosensory cortex appeared normal in diffusion- and T(2)-weighted MRI images. In sham-operated rats simultaneous electrical stimulation of both forepaws led to similar activation of both somatosensory cortices, while in pMCAO animals given vehicle only the contralateral cortex showed an fMRI response. Similarly, in pMCAO rats treated with isradipine, functional activation following bilateral electrical stimulation was only detected in the contralateral somatosensory cortex despite the normal appearance of the ipsilateral cortex in MRI images. Furthermore, fMRI responses to pharmacological stimulation with bicuculline were virtually absent in the ipsilateral somatosensory cortices both in vehicle- and isradipine-treated rats. Finally there was no significant difference between vehicle- and isradipine-treated animals upon the performance of beam-walking test or in forelimb grip strength. It is concluded that during the acute (24 h) post-occlusion period, structural integrity in the somatosensory cortex revealed by MRI does not translate into preservation of function.

Adenosine Triphosphate↗

From the diffusion coefficient to the diffusion tensor.

With diffusion tensor MRI one has access to the organization in space of tissue microstructural components. This outstanding potential adds, however, another layer of complexity to the diffusion MRI data acquisition and analysis processes. Over the last few years many articles have been published dealing with those matters. This special issue is thus timely to provide readers with the synthesis and the overall viewpoints from leading contributors to the field.

Anisotropy↗