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Diffusion-weighted MRI used to detect in vivo modulation of cortical spreading depression: comparison of sumatriptan and tonabersat.

Spreading cortical depolarization and depression of electroencephalographic activity (SD) may underlie the aura and spreading neurovascular events of migraine. Cortical depolarization may also precipitate the progressive development of cerebral pathology following ischemia. However, data on SD in the human brain are sparse, most likely reflecting the technical difficulties involved in performing such clinical studies. We have previously shown that the transient cerebral water disturbances during SD can be quantitatively investigated in the gyrencephalic brain using repetitive diffusion-weighted magnetic resonance imaging (DWI). To investigate whether DWI could detect modulation of the spatiotemporal properties of SD in vivo, the effects of the antimigraine drug sumatriptan (0.3 mg/kg iv) and the novel anticonvulsant tonabersat (10 mg/kg ip) were evaluated in the cat brain. Supporting previous findings, sumatriptan did not affect the numbers of events (range, 4-8), the duration of SD activity (39.8 +/- 4.4 min, mean +/- SEM), and event velocity (2.2 +/- 0.4 mm min(-1)); tonabersat significantly reduced SD event initiation (range, 0-3) and duration (13.2 +/- 5.0 min) and increased primary event velocity (5.4 +/- 0.7 mm min(-1)). However, both drugs significantly decreased, by >50%, the spatial extent of the first KCl-evoked SD event, and sumatriptan significantly increased event propagation across the suprasylvian sulcus (5.5 +/- 0.6 vs 2.4 +/- 0.4 events in controls). These results demonstrate (1) the feasibility of using DWI to evaluate therapeutic effects on SD, and (2) that sumatriptan may directly modulate the spatial distribution of SD activity in the gyrencephalic brain.

Animals↗

White matter asymmetry in the human brain: a diffusion tensor MRI study.

Language ability and handedness are likely to be associated with asymmetry of the cerebral cortex (grey matter) and connectivity (white matter). Grey matter asymmetry, most likely linked to language has been identified with voxel-based morphometry (VBM) using T(1)-weighted images. Differences in white matter obtained with this technique are less consistent, probably due to the relative insensitivity of the T(1) contrast to the ultrastructure of white matter. Furthermore, previous VBM studies failed to find differences related to handedness in either grey or white matter. We revisited these issues and investigated two independent groups of subjects with diffusion-tensor imaging (DTI) for asymmetries in white matter composition. Using voxel-based statistical analyses an asymmetry of the arcuate fascicle was observed, with higher fractional anisotropy in the left hemisphere. In addition, we show differences related to handedness in the white matter underneath the precentral gyrus contralateral to the dominant hand. Remarkably, these findings were very robust, even when investigating small groups of subjects. This highlights the sensitivity of DTI for white matter tissue differences, making it an ideal tool to study small patient populations.

Adult↗

Effects of oxygen and glucose deprivation on the expression and distribution of neuronal and inducible nitric oxide synthases and on protein nitration in rat cerebral cortex.

Changes in the nitric oxide (NO) system of the rat cerebral cortex were investigated by immunohistochemistry, immunoblotting, NO synthase (NOS) activity assay, and magnetic resonance imaging (MRI) in an experimental model of global cerebral ischemia and reperfusion. Brains were perfused transcardially with an oxygenated plasma substitute and subjected to 30 minutes of oxygen and glucose deprivation, followed by reperfusion for up to 12 hours with oxygenated medium containing glucose. A sham group was perfused without oxygen or glucose deprivation, and a further group was treated with the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) before and during perfusion. Global ischemia led to cerebrocortical injury as shown by diffusion MRI. This was accompanied by increasing morphologic changes in the large type I interneurons expressing neuronal NOS (nNOS) and the appearance of nNOS immunoreactivity in small type II neurons. The nNOS-immunoreactive band and calcium-dependent NOS activity showed an initial increase, followed by a fall after 6 hours of reperfusion. Inducible NOS immunoreactivity appeared in neurons, especially pyramidal cells of layers IV-V, after 4 hours of reperfusion, with corresponding changes on immunoblotting and in calcium-independent NOS activity. Immunoreactive protein nitrotyrosine, present in the nuclear area of neurons in nonperfused controls and sham-perfused animals, showed changes in intensity and distribution, appearing in the neuronal processes during the reperfusion period. Prior and concurrent L-NAME administration blocked the changes on diffusion MRI and attenuated the morphologic changes, suggesting that NO and consequent peroxynitrite formation during ischemia-reperfusion contributes to cerebral injury.

Animals↗

[Central pontine myelinolysis with a hyperintense lesion in diffusion weighted MRI: overview by means of a case report].

Central pontine myelinolysis (CPM) is a demyelinating disease of the pons often associated with demyelination of other areas of the central nervous system (CNS). The etiology and pathogenesis of this disorder are still not fully understood. However, almost all cases of CPM are related to severe diseases or chronic alcoholism and occur in the setting of rapidly corrected serum hyponatremia and hypotonicity respectively. Depending on the involvement of other CNS structures, the clinical picture can vary considerably. Magnetic resonance imaging is the most sensitive investigation for the antemortem diagnosis of CPM, although the radiological findings lag behind and do not necessarily correlate with the clinical picture. Quite obviously diffusion-weighted imaging can be useful in the rapid diagnosis of CPM. This short review summarizes the current knowledge on the pathogenesis, clinical presentation, radiological findings, prognosis and therapeutic approaches of CPM. Characteristical clinical features and MR-findings including hyperintensity on diffusion-weighted images are illustrated by a typical case.

Diffusion Magnetic Resonance Imaging↗

Megalencephalic leukoencephalopathy with subcortical cysts in an adult: quantitative proton MR spectroscopy and diffusion tensor MRI.

A 37-year-old macrocephalic woman was investigated for increasing gait disturbance due to longstanding spasticity and ataxia. MRI showed widespread bilateral increase in signal from cerebral white matter on T2-weighted images. Numerous subcortical cysts were visible in anterior-temporal and parietal regions. These clinical and neuroradiological features are those of megalencephalic leukoencephalopathy with subcortical cysts (MLC), a recently delineated white-matter disease with onset in childhood. Quantitative localised proton MR spectroscopy of white matter revealed marked reduction of N-acetylaspartate, creatine, and choline with normal values for myo-inositol, consistent with axonal loss and astrocytic proliferation. Diffusion tensor imaging showed an increased apparent diffusion coefficient and reduced anisotropy in affected white matter pointing to reduced cell density with an increased extracellular space. These findings are in line with histological changes alterations known to occur in MLC.

Adult↗

Combined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent endogenous activator of the cell death pathway and functions by activating the cell surface death receptors 4 and 5 (DR4 and DR5). TRAIL is nontoxic in vivo and preferentially kills neoplastically transformed cells over normal cells by an undefined mechanism. Radiotherapy is a common treatment for breast cancer as well as many other cancers. Here we demonstrate that ionizing radiation can sensitize breast carcinoma cells to TRAIL-induced apoptosis. This synergistic effect is p53-dependent and may be the result of radiation-induced up-regulation of the TRAIL-receptor DR5. Importantly, TRAIL and ionizing radiation have a synergistic effect in the regression of established breast cancer xenografts. Changes in tumor cellularity and extracellular space were monitored in vivo by diffusion-weighted magnetic resonance imaging (diffusion MRI), a noninvasive technique to produce quantitative images of the apparent mobility of water within a tissue. Increased water mobility was observed in combined TRAIL- and radiation-treated tumors but not in tumors treated with TRAIL or radiation alone. Histological analysis confirmed the loss of cellularity and increased numbers of apoptotic cells in TRAIL- and radiation-treated tumors. Taken together, our results provide support for combining radiation with TRAIL to improve tumor eradication and suggest that efficacy of apoptosis-inducing cancer therapies may be monitored noninvasively, using diffusion MRI.

Animals↗

[Transient ischemic attacks in the elderly: new definition and diagnostic difficulties].

Transient ischemic attacks (TIA) are very frequent in the elderly. Their frequency increases beyond 65 years. However, no epidemiologic study was specifically dedicated to elderly patients. The first definition of TIA was a sudden focal neurologic deficit that lasted for less than 24 hours, presumed to be of vascular origin and located in a specific artery territory of the brain or eye. The Working Study Group has proposed a new definition: TIA is a brief episode of neurologic dysfunction caused by focal brain or retinal ischemia with clinical symptoms typically lasting less than one hour, most often some minutes, and without evidence of acute infarction. Weighted diffusion MRI may show very early an aspect of cytotoxic oedema. The one-hour criterion associated with a stable neurological deficit is requested for initiating IV thrombolysis, if the angio-MRI shows an occlusion of the supra-aortic trunks or intracranial arteries, even in aged patients. Each TIA constitutes a major risk for a completed infarct resulting in disability or death. Hypertension is the main risk factor for TIAs, followed by atrial fibrillation, diabetes, coronaropathy and sedentarity. These factors multiply by 4 the stroke risk. In the elderly, TIAs are pecularly associated with lacunar infarcts in the territory of deep perforating arteries. TIAs represent a neurologic emergency that allows no delay in clinical and laboratory investigations, such as ultrasonic echographies and weighted diffusion MRI. Diagnostic errors are often due to frequent polypathology and cognitive changes in great age. The most misleading symptoms are vertigo, imbalance, falls, disorders of consciousness. Unawareness of the deficit is also a frequent cause of failure of TIA diagnosis. Conversely, the most frequent cause of diagnostic error by excess is epileptic seizures which are often under-evaluated.

Aged↗

Extraction and validation of correlation lengths from interstitial velocity fields using diffusion-weighted MRI.

Magnetic Resonance Imaging methods sensitive to individual molecular displacements (q-space MRI) provide a convenient means of measuring dispersion in complex interstitial spaces. Pressure-driven flow experiments through a water-saturated packed bed phantom have been conducted to prove the feasibility of using q-space MRI to measure the coherence length associated with the interstitial velocity field. The method involves measuring the dependence of the apparent dispersion coefficient on the distance along the mean flow by repeating a small number of pulsed-gradient stimulated-echo experiments with increasing gradient pulse separation times. Assuming homogeneous interstitial flow statistics inside the averaging volume, an integral spatial scale characterizing the Eulerian velocity auto-correlation coefficient is extracted via a stochastic convective model. The validity of the a priori statistical description of interstitial flow is verified by comparing with an independent MRI measurement of the Eulerian velocity field using phase contrast methods in the same phantom with pore-level resolution. The integral length scale obtained via q-space MRI agrees with the mean pore size in the present as well as in similar phantoms found in the literature. This method has direct applicability in the quantification of the interstitial morphology of fluid-saturated porous media with resolution independent of voxel size, assuming "perfectly reflecting pore walls" (no surface relaxation) and no contribution to the MR signal from outside the pore space.

Diffusion Magnetic Resonance Imaging↗

Newer imaging modalities to assess tumor in the prostate.

BACKGROUND: Several advances in the imaging of prostate cancer have been made in recent years. Diagnostic staging has become increasingly complex and confusing as newer technologies have developed more rapidly than research has been able to confirm or refute the accuracy of these technologies. By the time research has been performed, the technology used for a study has often become outdated and newer and more sophisticated imaging has become available. METHODS: We reviewed the literature on local and nodal staging of prostate cancer, as well as the role of magnetic resonance imaging (MRI), magnetic resonance spectroscopic imaging (MRSI), dynamic contrast-enhanced MRI, positron emission tomography (PET), endorectal power Doppler, lymphotropic MRI contrast agents, and future possibilities such as diffusion MRI. This review is not systematic, but rather focused on these imaging modalities. RESULTS: Advances in MRI, ultrasound, and lymphotropic contrast agents have improved our ability to differentiate between T2 and T3 prostate tumors. PET imaging has proven less successful at staging prostate cancer. A literature review suggests patients with moderate risk of extracapsular extension benefit most from endorectal MRI evaluation. Spectroscopy, dynamic imaging, and lymphotropic contrast agents are expected to continue to improve sensitivity and specificity of staging of prostate cancer. Power Doppler evaluation with endorectal ultrasound has proved useful for evaluation during endorectal biopsy for identifying hypervascular tumors for directed biopsy. Diffusion-weighted MRI remains untested clinically and represents a future direction for research. CONCLUSIONS: Future studies using these new techniques are needed to demonstrate changes in outcomes in large patient populations.

Contrast Media↗

[Serial diffusion-weighted MRI (DWI) in a patient with sporadic Creuztfeldt-Jakob disease].

Serial DWIs were performed in a patient with CJD who developed symptoms acutely and progressed rapidly. DWI discloed an increased signal in the frontal and parietal inner cortical areas, and in the caudate nuclei and putamina 20 days after the onset of symptoms. T2-weighted images showed only signal abnormality in the caudate nuclei and putamina, but not in the cerebral cortex. In the CSF obtained 15 days after the onset of symptoms, total tau protein was markedly elevated and 14-3-3 protein was positive. Measurement of these proteins are highly specific and sensitive for the diagnosis of CJD, but not available as a rapid routine examination at present. DWI is not specific, but useful for making the diagnosis of CJD in the early stage of the disease.

Aged↗

A measure of curve fitting error for noise filtering diffusion tensor MRI data.

A parameter, chi2p, based on the fitting error was introduced as a measure of reliability of DT-MRI data, and its properties were investigated in simulations and human brain data. Its comparison with the classic chi2 revealed its sensitivity to both the goodness of fit and the pixel signal-to-noise-ratio (SNR), unlike the classic chi2, which is sensitive only to the goodness of fit. The new parameter was thus able to separate effectively pixels with coherent signals (having small fitting error and/or high SNR) from those with random signals (having inconsistent fitting and/or low SNR). A practical advantage of chi2p over the classic chi2 was that chi2p is quantified directly from the data of each pixel, without requiring accurate estimation of data-dependent parameters (such as noise variance), which often makes application of the classic chi2 problematic. Analytical approximations of chi2p enabled an objective (data-independent) and automated calculation of a threshold value, used for internal scaling of the chi2p map. Apart from assessing data reliability on a pixel-by-pixel basis, chi2p was used to develop an objective and generic methodology for the exclusion of pixels with unreliable DT information by discarding pixels with chi2p values exceeding the threshold. Pixels corresponding to very low SNR, and poorly fitted cerebrospinal fluid and surrounding brain tissue, had increased chi2p values and were successfully excluded, providing DT anisotropy maps free from artifactual anisotropic appearance.

Adult↗

Simultaneous temperature and regional blood volume measurements in human muscle using an MRI fast diffusion technique.

The thermal dependence of the translational diffusion coefficient and of the regional blood volume was investigated in vivo by using a special MR pulsed gradient technique with reduced sensitivity to bulk tissue motion. Measurements were done at 0.5 T, using a small gradient insert. The diffusion coefficient of muscle water was calibrated against thermocouple-measured temperature in vitro, both with the muscle fibers parallel and perpendicular to the diffusion gradient. The maximum muscle temperature variation obtained by percutaneous conduction was -8.8 +/- 1.6 degrees C under cooling and +3.7 +/- 1.6 degrees C under heating, from basal state. Simultaneously the fractional regional blood volume decreased by a factor of 3.5 under cooling and increased by a factor of 2.7 under heating. Due to the interdependence of microcirculation and tissue temperature, this technique may be used to follow heat production or deposition in living tissue (muscle exercise, electromagnetic irradiation, etc.).

Artifacts↗

Cost containment and diffusion of MRI: oil and water?. Japanese experience.

The total number of MR units available in Japan relative to the population is the highest in the world. The total number of MR units installed in 1996 was 2,663, equivalent to 24 per million population. The average charge per procedure in Japan is only one fifth of that in the United States (USA), approximately US$200 and US$950, respectively, suggesting that economic considerations in Japan may not take the highest priority. Despite the low costs, the utilisation (the number of patients examined each year or per week) of MR units in Japan is only about half that in the USA. As such, an increase in the number of MR units per se does not result in excessive health care costs.

Cost Control↗

Cost containment and diffusion of MRI: oil and water?. The situation in Europe.

Investments in diagnostic imaging in European countries range between 2.2 and 5.4 % of gross national product, a figure which, in view of new imaging modalities and increased radiological density, is considered to be wholly inadequate. Despite the fact that radiological examinations contribute more than laboratory tests and other diagnostic modalities to the final clinical diagnosis, and that MR is of increasing clinical relevance, economic constraints mean that the number of new MRI installations in Europe is decreasing relative to the situation elsewhere. The present article discusses the current state of radiological imaging in Europe with particular emphasis on present and expected future trends in MRI.

Cost Control↗

Acquisition of spin echo and stimulated echo by a single sequence: application to MRI of diffusion.

A new method is described to measure the restricted diffusion coefficient with magnetic resonance imaging. The two images necessary to calculate the diffusion image are obtained with a simultaneous acquisition of a spin-echo and a stimulated echo, and so, in half the time needed by usual spin-echo or stimulated echo method. A different diffusion contrast is created on each echo. A map of an estimate of the diffusion coefficient and an estimation of T1 value are obtained with only one experiment. The accuracy of the method has been evaluated on phantom and results are in agreement with values found in previous papers and with measurements performed with a usual spin-echo method. Furthermore, in vivo measurements have shown that this method can be used without electrocardiogram triggering.

Brain↗