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Vascular disease, mainly atherosclerosis, is a major cause of death and disability in the Western world. As a generalized process it involves nearly all vascular territories, and the incidence increases with age. Responsible for different severe clinical findings, it is also the major cause of cerebrovascular disease. In the CNS it is the main cause of stroke, which is fatal in about 40% of cases [1]. However, every year approximately 20 million people worldwide survive stroke, making it a major cause of disability as well. Many of the stroke survivors are left with significant permanent disability [2] that requires costly clinical care [3]. Although ischemia accounts for 80% of all strokes, in some instances it is caused by intracranial hemorrhage, usually secondary to rupture of an intracranial aneurysm or vascular malformations [4]. Atheromatous debris from focal atherosclerotic plaque, usually at the carotid bifurcation, is the most common identifiable cause of carotid artery stenosis [5], present in about 25% of all strokes [6]. In patients with significant stenoses (i.e., >70% luminal narrowing) there are a variety of therapeutic options, including carotid endarterectomy or carotid stenting [7, 8, 9].

In 1907 Alois Alzheimer (1864–1915) described the case report of a woman who had presented with a history of progressive cognitive decline with disorientation, incomprehension, perseveration, dysphasia, dysgraphia and dyspraxia, accompanied by psychopathological symptoms such as delusions and hallucinations at age 51 (Alzheimer 1907). She died 4.5 years after her admission to the Frankfurt Asylum for Lunatics and Epileptics. The postmortem examination revealed cerebral extracellular plaques and intracellular neurofibrillary bundles — Alzheimersche Fibrillen — i.e. those changes which are generally recognized to represent the hallmarks of the disease. As proposed by E. Kraepelin in the 8th edition of his textbook, the condition was subsequently named after Alzheimer.

Vasovist® (Gadofosveset, Bayer Schering Pharma AG, Berlin, Germany) represents a third generation of contrast agents. It is the first approved MR contrast medium with a pronounced and reversible protein binding, resulting in a long blood half-life. The agent is categorized as an intravascular or blood pool agent and was developed for MR angiographic applications, allowing imaging in a submillimeter resolution range in the equilibrium phase.

MRI in neuroradiology has evolved in the last 30 years, becoming faster, more precise, and more specific. The latest additions, including magnetic resonance spectroscopy (MRS), diffusion imaging, diffusion tensor imaging, functional MRI, and dynamic susceptibility contrast perfusion imaging, have expanded the applications for MR imaging. Currently, fluid attenuation inversion recovery (FLAIR) imaging, thin-section 3D volumetric imaging with spoiled gradient techniques, and the others mentioned above permit not only the precise localization of brain lesions, but also the evaluation of their metabolic profile, their location relative to eloquent regions of the cortex and subcortical white matter, and the relative blood volume and permeability of the vasculature that supplies the lesion. Thus, cellular, vascular, functional and anatomic information are obtained in one examination session and are available to treating physicians in their office, operating room, or radiation therapy suite.

Rationale and Objectives Malignant mesothelioma (MM) of the pleura is an aggressive and often fatal neoplasm. Because MM frequently demonstrates marked angiogenesis, it may be responsive to antiangiogenic therapy, but effective methods for selecting and monitoring of patients are further needed. We employed dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and quantitative immunohistochemistry (IHC) to characterize the microvascularity of MM using both a physiologic and ultrastructural method. Materials and Methods Nineteen patients diagnosed with MM were enrolled and DCE-MRI was performed before antiangiogenic treatment. For each patient, tumor regions were characterized by their DCE-MRI–derived pharmacokinetic parameters (Amp, k ep , k el ), which were also compared to those of normal tissue (aorta, liver, spleen, and muscle). In addition, quantitative IHC of representative samples was performed with CD-34 staining to compare the calculated microvessel density (MVD) results with DCE-MRI results. Results MM demonstrated markedly abnormal pharmacokinetic properties compared with normal tissues. Among the parameters tested, Amp was significantly different in MM ( P ≤ .001) compared to normal organs. Despite the observation that the MVD of mesotheliomas in this series was high compared to other tumors, DCE-MRI pharmacokinetic parameters had a moderately positive correlation with MVD ( r = 0.5). Conclusions DCE-MRI and IHC can be used in patients with MM to visualize tumor microvascularity and to characterize tumor heterogeneity. DCE-MRI and IHC results positively correlated, though moderately, but these two methods present as essential tumor biomarkers. This multimodal characterization may be useful in selecting possible tumor subtypes that would benefit from antiangiogenic therapy.

PURPOSE To assess metabolism and microcirculation of healthy skeletal muscle by magnetic resonance (MR) and ultrasound techniques and to compare these data with muscle histology, and anthropometric and blood parameters. METHODS Thirty-four healthy volunteers were selected such that their measured aerobic capacity (VO2max) per body weight ranged between 23 and 66 mL/minute/kg to render a large variability of skeletal muscle capillarization as a result of their different physical activity. We analyzed body composition, blood parameters, and skeletal muscle fiber size and capillarization in biopsies of the vastus lateralis muscle. These data were compared with knee extensor cross-sectional area (CSA) obtained by MR imaging, microcirculation of the vastus lateralis muscle by contrast-enhanced ultrasound (CEUS), and its energy and lipid metabolism measured with 31P and 1H MR spectroscopy. Statistical analysis was performed using Pearson's correlation coefficient and significance was tested at a level of .5%. RESULTS The variable physical activity was reflected in a large variability of vastus lateralis muscle perfusion and metabolism at rest with highest histologic capillarization and CEUS-perfusion values observed in the best-trained volunteers. Levels of high-energy phosphates, such as phosphocreatine, were positively correlated with CSA (r= .5) and histologic fiber size (r= .6 for type IIA and IIX fibers), while phosphocreatine concentration was significantly negatively correlated to myocellular lipids (r=−.6) and trimethyl ammonium containing compounds (r=−.8). Local blood volume measured in vivo with CEUS was positively correlated with several histologic capillarization parameters. CONCLUSIONS Dedicated MR- and CEUS-methods deliver (patho-)physiologic information about capillarization and fiber characteristics of skeletal muscles in vivo and hence establish a useful diagnostic tool for muscular diseases.

Stroke, a major cause of death and disability in the developed world, is usually caused by atherosclerosis, most commonly an arterioocclusive lesion at the carotid bifurcation. Numerous multicentre trials have demonstrated that carotid endarterectomy can reduce the risk of stroke in these patients. However, because of the morbidity of catheter angiography coupled with the risks of surgery, the benefits outweigh the risks of surgery only for those with70% carotid artery stenosis. The gold standard method for assessing the degree of stenosis is catheter-directed cerebral digital subtraction angiography; however, this is associated with a small but substantial stroke risk in addition to inherent risks associated with use of ionizing radiation and nephrotoxic contrast agents. The requirement for alternative imaging techniques that do not contribute to morbidity is ideally met by contrast-enhanced magnetic resonance angiography, which eliminates the need for direct catheterization and therefore eliminates stroke risk associated with a patient work-up. Advances in contrast-enhanced magnetic resonance angiography technology have led to a technique that achieves the goals of high spatial and temporal resolution required for stenosis assessment and streamlining of patients along surgical or medical lines. With the advent of a novel contrast agent, gadofosveset trisodium (Vasovist, Bayer Schering Pharma AG, Berlin, Germany), which has a high relaxivity and an extended imaging time, improved diagnosis of carotid artery stenoses with magnetic resonance angiography can be expected. Gadofosveset trisodium facilitates improved first-pass imaging and also delays steady-state imaging with one injection. Although developed for vascular imaging, gadofosveset trisodium may also allow assessment of brain vascularity, blood-brain barrier breakdown and neurodegenerative disease.

Neuropathological research consistently revealed the cerebellum to undergo degenerative changes in Alzheimer's disease (AD). Whether these alterations affect cerebellar morphology in vivo has not yet been investigated in a comprehensive way. Magnetic resonance imaging was performed in 20 patients with AD, 20 with mild cognitive impairment (MCI), and 20 healthy controls. By manual tracing the cerebellum was divided in four substructures (anterior lobe, superior posterior lobe, inferior posterior lobe and corpus medullare, respectively) on each hemisphere. Posterior cerebellar lobes were significantly smaller in AD patients when compared to healthy controls. In the AD group, atrophy of the posterior cerebellar regions was associated with poorer cognitive performance. Our findings lend further support for cerebellar involvement in AD.

Abnormalities in limbic-thalamic-cortical networks are hypothesized to modulate human mood states. In the present study differences in hippocampal volumes of patients with a first episode of depression, recurrent major depression and healthy control subjects were examined with high-resolution magnetic resonance imaging (MRI). Male patients with a first episode of major depression had a significantly smaller left hippocampal volume than male control subjects. Also, these patients had a significant left-right asymmetry in hippocampal volume. Female patients showed no significant alterations in hippocampal volumes. The results support the hypothesis that the hippocampus plays an important role in the pathophysiology of the early phase of major depression, especially for male patients. Implications for the neurodevelopmental and the neurodegenerative model of hippocampal change are discussed.

Brain tumors are one of the most common neoplasms in young adults and are associated with a high mortality and disability rate. Magnetic resonance imaging (MRI) is widely accepted to be the most sensitive imaging modality in the assessment of cerebral neoplasms. Because the detection, characterization, and exact delineation of brain tumors require a high lesion contrast that depends on the signal of the lesion in relation to the surrounding tissue, contrast media is given routinely. Anatomical and functional, contrast agent-based MRI techniques allow for a better differential diagnosis, grading, and especially therapy decision, planing, and follow-up. In this article, the basics of contrast enhancement of brain tumors will be reviewed. The underlying pathology of a disrupted blood-brain barrier and drug influences will be discussed. An overview of the currently available contrast media and the influences of dosage, field strength, and application on the tumor tissue contrast will be given. Challenging, contrast-enhanced, functional imaging techniques, such as perfusion MRI and dynamic contrast-enhanced MRI, are presented both from the technical side and the clinical experience in the assessment of brain tumors. The advantages over conventional, anatomical MRI techniques will be discussed as well as possible pitfalls and drawbacks.

To prospectively examine whether sodium 23 (23Na) magnetic resonance (MR) imaging can be used to visualize acute intracellular Na+ accumulation and the effects of specific therapy in patients with paramyotonia congenita (PC).Ethics committee approval and informed consent were obtained. Sixteen patients (four women, 12 men; mean age, 46.7 years +/- 16.7 [standard deviation]) with confirmed PC and 10 healthy volunteers (three women, seven men; mean age, 26.6 years +/- 3) were examined by using a 1.5-T MR system with a 16.8-MHz surface coil. 23Na MR imaging was performed before and after local cooling of the nondominant lower leg and exercising, with experimentally induced weakness scored by a neurologist. The 23Na MR examination was repeated in 13 patients and all volunteers after 3 days and, additionally, in seven patients after 4 days of oral administration of mexiletine, which blocks Na+ channels. The 23Na MR protocol comprised two-dimensional (2D) fast low-angle shot (FLASH), 2D radial, and free induction decay (FID) sequences. The FID data were fitted to a biexponential decay curve to evaluate the slow and fast components of the T2 relaxation time. Fast and slow components were assigned to intra- and extracellular Na+ concentrations, respectively. Radial and FLASH MR images were evaluated by means of a region-of-interest analysis by using 0.3% saline solution for reference. T1- and T2-weighted MR imaging were also performed. Data were analyzed by using a parametric t test.After exercising, all patients developed considerable weakness exclusively in the cooled lower leg; no weakness was observed in volunteers. In patients, all 23Na MR images showed a significant increase in 23Na signal intensity in the cooled lower leg (P.001) in comparison with nonsignificant findings in volunteers. After treatment with mexiletine, cooling and exercise induced almost no muscle weakness and no changes in 23Na MR signal intensity in patients.23Na MR imaging enables visualization of muscular Na+ accumulation associated with muscle weakness in patients with PC, and effects of specific therapy can be detected.

The challanging and multiple goals and requirements of CNS tumor imaging require optimization of the CNS imaging protocols, including selection of the optimal contrast medium. There are several gadolinium compounds available for imaging the CNS, and all of these except the compound Gd-BOPTA have nearly identical profiles. The unique protein interaction of Gd-BOPTA results in double T1 and T2 relaxivity. This article summarizes the advantages of Gd-BOPTA over conventional gadolinium compounds in both conventional and functional MR imaging. The results of recent studies in adults and pediatric patients are presented and discussed. The principal conclusion of this article is that not all contrast agents approved for MR imaging of the CNS behave in the same way. The use of the high-relaxivity agent Gd-BOPTA for morphological and functional MR imaging allows improved detection and delineation of CNS lesions compared to conventional gadolinium agents. This not only permits more confident diagnoses, but also results in a substantially improved differential diagnostic process. The higher relaxivity of Gd-BOPTA helps to optimize functional MR imaging studies e.g. perfusion MR imaging and other dynamic MR imaging protocols.

Malignant gliomas remain incurable brain tumors because of their diffuse-invasive growth. So far, the genetic and molecular events underlying gliomagenesis are poorly understood. In this study, we have identified the receptor tyrosine kinase Axl as a mediator of glioma growth and invasion. We demonstrate that Axl and its ligand Gas6 are overexpressed in human glioma cell lines and that Axl is activated under baseline conditions. Furthermore, Axl is expressed at high levels in human malignant glioma. Inhibition of Axl signaling by overexpression of a dominant-negative receptor mutant (AXL-DN) suppressed experimental gliomagenesis (growth inhibition >85%, P < 0.05) and resulted in long-term survival of mice after intracerebral glioma cell implantation when compared with Axl wild-type (AXL-WT) transfected tumor cells (survival times: AXL-WT, 10 days; AXL-DN, >72 days). A detailed analysis of the distinct hallmarks of glioma pathology, such as cell proliferation, migration, and invasion and tumor angiogenesis, revealed that inhibition of Axl signaling interfered with cell proliferation (inhibition 30% versus AXL-WT), glioma cell migration (inhibition 90% versus mock and AXL-WT, P < 0.05), and invasion (inhibition 62% and 79% versus mock and AXL-WT, respectively; P < 0.05). This study describes the identification, functional manipulation, in vitro and in vivo validation, and preclinical therapeutic inhibition of a target receptor tyrosine kinase mediating glioma growth and invasion. Our findings implicate Axl in gliomagenesis and validate it as a promising target for the development of approaches toward a therapy of these highly aggressive but, as yet, therapy-refractory, tumors.

To prospectively compare gadobenate dimeglumine with gadopentetate dimeglumine (0.1 mmol per kilogram body weight) for enhanced magnetic resonance (MR) imaging of central nervous system (CNS) lesions.This study was HIPAA-compliant at U.S. centers and was conducted at all centers according to the Good Clinical Practice standard. Institutional review board and regulatory approval were granted; written informed consent was obtained. Seventy-nine men and 78 women (mean age, 50.5 years +/- 14.4 [standard deviation]) were randomized to group A (n = 78) or B (n = 79). Patients underwent two temporally separated 1.5-T MR imaging examinations. In randomized order, gadobenate followed by gadopentetate was administered in group A; order of administration was reversed in group B. Contrast agent administration (volume, speed of injection), imaging parameters before and after injection, and time between injections and postinjection acquisitions were identical for both examinations. Three blinded neuroradiologists evaluated images by using objective image interpretation criteria for diagnostic information end points (lesion border delineation, definition of disease extent, visualization of internal morphologic features of the lesion, enhancement of the lesion) and quantitative parameters (percentage of lesion enhancement, contrast-to-noise ratio [CNR]). Overall diagnostic preference in terms of lesion conspicuity, detectability, and diagnostic confidence was assessed. Between-group comparisons were performed with Wilcoxon signed rank test.Readers 1, 2, and 3 demonstrated overall preference for gadobenate in 75, 89, and 103 patients, compared with that for gadopentetate in seven, 10, and six patients, respectively (P.0001). Significant (P.0001) preference for gadobenate was demonstrated for diagnostic information end points, percentage of lesion enhancement, and CNR. Superiority of gadobenate was significant (P.001) in patients with intraaxial and extraaxial lesions.Gadobenate compared with gadopentetate at an equivalent dose provides significantly better enhancement and diagnostic information for CNS MR imaging.

Ziele: Die MRS bietet die Moglichkeit nichtinvasiv Aussagen uber den Zell-Metabolismus in-vivo zu treffen. In diesem Lehrposter soll die klinische Anwendung der 31P-MRS am Beispiel der Darstellung von energiereichen 31P-Metaboliten am ruhenden und isometrisch angespannten Oberschenkel-Muskel (M. vastus lat.) vorgestellt werden. Methode: Alle Messungen wurden an einem 1.5T-MRT (Magnetom Vision, Siemens) durchgefuhrt. Die Signalakquisition erfolgte mittels einer doppelresonanten 1H-/31P- planaren Oberflachenspule, die direkt am Oberschenkel des Patienten/Probanden positioniert und individuell abgestimmt wurde. Durch manuellen Shim (Optimierung der Homogenitat des statischen Magnetfeldes) wurde eine Linienbreite der Wasserresonanz von typischen 30Hz erreicht. Die 31P-MRS erfolgte mit einer nicht ortsaufgelosten Free-Induction-Decay (FID) Sequenz (TR=1100 ms) mit einer Messdauer von ca. 10min. Fur Messungen unter isometrischer Anspannung des Muskels wurde hierbei die Zahl der Akquisitionen so weit reduziert, dass sich eine Zeitauflosung von ca. 20s ergab. Die Auswertung der Spektren erfolgte mittels der Nachverarbeitungssoftware des Scanners (LUISE®). Ergebnis: Die 31P-MRS ermoglichte die Darstellung folgender Resonanzen der 31P-Metaboliten: alpha-, betha- und gamma-ATP, anorganische Phosphate (Pi) und Phosphokreatin (PCr). Zusatzlich lasst sich aus dem Frequenz-Abstand von PCr und Pi der pH-Wert bestimmen. So schlagt sich z.B. die Ubersauerung des Muskels bei Muskelaktivitat im pH-Wert nieder. Im Vergleich zu gesunden Probanden konnten bei Patienten mit Erkrankungen der Muskulatur, die mit Defekten der Energiespeicher einhergehen (Muskelatrophien) eine Abnahme des PCr und der Pi beobachtet werden. Schlussfolgerung: Die vorgestellte Methodik ist ein im klinischen Alltag einsetzbares Verfahren, das es ermoglicht nichtinvasiv Veranderungen an Energiemetaboliten zu beobachten, deren Ursprung in pathologischen und physiologischen Prozessen in der Skelettmuskulatur begrundet sind. Korrespondierender Autor: Hertel R DKFZ. Heidelberg, E 010, Plock 2, 69198, Schriesheim E-Mail: r.hertel@dkfz.de

Gadobenate dimeglumine (Gd-BOPTA) possesses a two-fold higher T1 relaxivity compared to other available gadolinium contrast agents. The study was conducted to evaluate the benefits of this increased relaxivity for MR imaging of intracranial enhancing brain lesions.Forty-five patients (31 males, 14 females) with suspected glioma or cerebral metastases were evaluated. Patients received Gd-BOPTA and either Gd-DTPA (n = 23) or Gd-DOTA (n = 22) in fully randomized order at 0.1 mmol/kg body weight and at a flow rate of 2 ml/s. The second agent was administered 1-14 days after the first agent. Images were acquired precontrast (T1wSE, T2wFSE sequences) and at sequential postcontrast time-points (T1wSE sequences at 0, 2, 4, 6, and 8 and 15 min and a T1wSE-MT sequence at 12 min) at 1.0 or 1.5 T using a head coil. Determination of contrast enhancement was performed quantitatively (lesion-to-brain ratio, contrast-to-noise ratio, and percent enhancement) and qualitatively (border delineation, internal morphology, contrast enhancement, and diagnostic preference) by two independent, fully blinded readers.Images from 43/45 patients were available for quantitative assessment. After correction for precontrast values, significantly greater lesion-to-brain ratio (P.003), contrast-to-noise ratio (P.03), and percent enhancement (P.0001) was noted by both readers for Gd-BOPTA-enhanced images at all time-points from 2 min postcontrast. Qualitative assessment of all patients similarly revealed significant preference for Gd-BOPTA for lesion border delineation (P.004), lesion internal morphology (P.008), contrast enhancement (P.0001), and diagnostic preference (P.0005).The greater T1 relaxivity of Gd-BOPTA permits improved visualization of intracranial enhancing lesions compared to conventional gadolinium agents.

The purpose of this study was to monitor liver metastases after radiotherapy using contrast-enhanced ultrasound (CEUS). In 15 patients, follow-up examinations after stereotactic, single-dose radiotherapy were performed using CEUS (low mechanical index (MI), 2.4-ml SonoVue) and computed tomography (CT). Besides tumor size, the enhancement of the liver and the metastases was assessed at the arterial, portal venous, and delayed phases. The sizes of the tumor and of a perifocal liver reaction after radiotherapy measured with CEUS significantly correlated with those measured at CT (r=0.93, p

We investigated whether observing the arterial vascularization of liver metastases by contrast-enhanced ultrasound with low mechanical index (low-MI) imaging offers additional diagnostic information for the characterization of the liver lesions.Twenty nine patients with untreated liver metastases of different primaries were examined. Measurements were performed using a low frame rate, low-MI pulse inversion technique after injection of 2.4 mL SonoVue. The relative maximum signal intensity of the liver lesions related to the normal liver tissue was quantified. Ultrasound findings were compared with contrast-enhanced, dual-phase computed tomography (CT) using a pattern-based classification scheme.Compared with contrast-enhanced CT, this modality better detects arterial perfusion. Metastases, even those usually considered hypovascularized, often showed homogeneous enhancement (66%) and higher arterial vascularization than normal liver tissue. CT did not show a comparable vascularization pattern (P0.001) or any similarly early signal intensity (P0.001).Contrast-enhanced CT may not be able to visualize short-lasting but large differences of the arterial perfusion of liver metastases, as does contrast-enhanced low-MI ultrasound. This offers new methods for their characterization and for monitoring of therapeutic effects.

The use of Gd-BOPTA as a contrast agent for morphological and functional MR imaging allows improved detection and delineation of CNS lesions compared with conventional gadolinium agents. This not only leads to more confident diagnoses being made, but also results in a substantially improved differential diagnostic process. The higher relaxivity of Gd-BOPTA helps to optimize functional MR imaging studies, for example, perfusion MR imaging and dynamic MR angiographic protocols.

Auf der Grundlage der Forschung der letzten Jahrzehnte, beginnend mit der Darstellung erweiterter Ventrikel mittels Pneumenzephalographie [25], ist es inzwischen unumstritten, dass bei Patientinnen mit Schizophrenie — insbesondere bei chronischem Verlauf — diskret bis masig ausgepragte morphologische Veranderungen von Hirnstrukturen vorliegen. Vor allem bildgebende Verfahren ermoglichen eine In-vivo-Erfassung dieser strukturellen Veranderungen, die konsistent nachweisbar sind, jedoch in weit geringerer Auspragung als bei neurodegenerativen Erkrankungen wie z.B. der Alzheimer-Demenz. In Vergleichsuntersuchungen schizophrener Patientinnen mit gesunden Kontrollpersonen finden sich daher haufig widerspruchliche Befunde hinsichtlich der Morphologie, insbesondere in Abhangigkeit vom Krankheitsstadium, dessen Einfluss auf die strukturellen Veranderungen letztendlich noch nicht vollstandig geklart ist.

The posterior fossa is the deepest and most capacious of the three cranial fossae (Burt 1993). It houses the brainstem and cerebellum. The brainstem contains all the cranial nerve nuclei and many efferent and afferent fiber tracts that connect the brain with the rest of the body. The cerebellum is the major organ of coordination for all motor functions, as well as mental activities of the brain. Located centrally in the posterior fossa is the foramen magnum. The posterior fossa is surrounded by deep grooves containing the transverse sinuses and sigmoid sinuses.

To evaluate late radiation effects in the brain after radiosurgery of patients with cerebral arteriovenous malformations (AVMs) and to quantify dose/volume-response relations for radiation-induced changes of brain tissue identified on follow-up neuroimaging.. Data from 73 AVM patients who had stereotactic Linac radiosurgery at DKFZ (German Cancer Research Center), Heidelberg, Germany, were retrospectively analyzed. The endpoint of radiation-induced changes of brain tissue on follow-up magnetic resonance (MR) neuroimaging (i.e., edema and blood-brain-barrier breakdown [BBBB]) was evaluated. Each endpoint was further differentiated into three levels with respect to the extent of the image change (small, intermediate, and large). A previous analysis of the data found correlation of the endpoints with several dose/volume variables (DV) derived from each patient's dose distribution in the brain, including the mean dose in a volume of 20 cm(3) (Dmean20) and the absolute brain volume (including the AVM target) receiving a dose of at least 12 Gy (V12). To quantify dose/volume-response relations, patients were ranked according to DV (i.e., Dmean20 and V12) and classified into four groups of equal size. For each group, the actuarial rates of developing the considered endpoints within 2.5 years after radiosurgery were determined from Kaplan-Meier estimates. The dose/volume-response curves were fitted with a sigmoid-shape logistic function and characterized by DV(50), the dose for a 50% incidence, and the slope parameter k.. Dose/volume-response relations, based on two alternative, but correlated, dose distribution variables that are a function of both dose and volume, were observed for radiation-induced changes of brain tissue. DV(50) values of fitted dose/volume-response curves for tissue changes of large extent (e.g., V12(50) = 22.0 +/- 2.6 cm(3) and Dmean20(50) = 17.8 +/- 2.0 Gy for the combined endpoint of edema and/or BBBB) were significantly higher than those for small tissue changes (V12(50) = 4.0 +/- 0.3 cm(3) and Dmean20(50) = 7.6 +/- 0.3 Gy).. The derived dose/volume-response relations allow to quantitatively assess the risk of radiation-induced changes of brain tissue after radiosurgery in AVM patients. However, further understanding of the mechanism leading to brain tissue changes and their correlation with the desired obliteration is required. This knowledge will eventually help to optimize radiosurgical treatments in AVM patients.

To evaluate relative cerebral blood flow (rCBF) in normal brain tissue using arterial spin-labeling (ASL) methods and first-pass dynamic susceptibility-weighted contrast-enhanced (DSC) magnetic resonance imaging (MRI).Sixty-two patients with brain metastases were examined on a 1.5 T-system up to 6 times during routine follow-up after stereotactic radiosurgery. Perfusion values in normal gray and white matter were measured using the ASL techniques ITS-FAIR in 38 patients, Q2TIPS in 62 patients, and the first-pass DSC echo-planar (EPI) MRI after bolus administration of gadopentetate dimeglumine in 42 patients. Precision of the ASL sequences was tested in follow-up examinations in 10 healthy volunteers.Perfusion values in normal brain tissue obtained by all sequences correlated well by calculating Pearson's correlation coefficients (P0.0001) and remained unchanged after stereotactic radiosurgery as shown by analysis of variance (P0.05).Both ASL and DSC EPI MRI yield highly comparable perfusion values in normal brain tissue.

Increased tau levels are a well-established finding in Alzheimer's disease (AD). In contrast, the potential value of tau levels in the differential diagnosis of AD, vascular dementia (VD) and major depression warrants further investigation. The potential impact of psychotropic medication also needs to be established. We investigated cerebrospinal fluid (CSF) tau protein concentrations in 88 patients with AD, 23 patients with VD, 25 patients with major depression and 17 age-paralleled controls without cognitive impairment with respect to important clinical variables, type and dosage of psychotropic medication and cerebral changes as assessed by magnetic resonance imaging (MRI). The AD patients showed significantly elevated tau levels compared with patients with VD or major depression and controls. Tau levels obtained in the VD group were intermediate, with significant differences from both AD patients and patients with major depression and controls. Within the AD group, no significant correlation between tau levels, severity of dementia, age, duration of disease, type and dosage of psychotropic medication or MRI volumetric changes arose. A subgroup of AD patients without increased tau levels was characterized by a significantly larger percentage of patients with presenile onset.

Advanced bronchial carcinomas by means of perfusion and peak enhancement using dynamic contrast-enhanced multislice CT are characterized. Twenty-four patients with advanced bronchial carcinoma were examined. During breathhold, after injection of a contrast-medium (CM), 25 scans were performed (1 scan/s) at a fixed table position. Density-time curves were evaluated from regions of interest of the whole tumor and high- and low-enhancing tumor areas. Perfusion and peak enhancement were calculated using the maximum-slope method of Miles and compared with size, localization (central or peripheral) and histology. Perfusion of large tumors (50 cm3) averaged over both the whole tumor (P = 0.001) and the highest enhancing area (P = 0.003) was significantly lower than that of smaller ones. Independent of size, central carcinomas had a significantly (P = 0.04) lower perfusion (mean 27.9 ml/min/100 g) than peripheral ones (mean 66.5 ml/min/100 g). In contrast, peak enhancement of central and peripheral carcinomas was not significantly different. Between non-small-cell lung cancers and small-cell lung cancers, no significant differences were observed in both parameters. In seven tumors, density increase after CM administration started earlier than in the aorta, indicating considerable blood supply from pulmonary vessels. Tumor perfusion was dependent on tumor size and localization, but not on histology. Furthermore, perfusion CT disclosed blood supply from both pulmonary and/or bronchial vessels in some tumors.

Purpose: To evaluate the long-term cognitive function of patients with cerebral arteriovenous malformations (AVMs) after radiosurgery. Methods and Materials: The data of 95 AVM patients were prospectively assessed up to 3 years after radiosurgery. Of these patients, 39 had a follow-up of at least 2 years. Radiosurgery was performed using a modified linear accelerator (minimal doses to the target volume 15–22 Gy, median dose 20). The neuropsychological evaluation included testing of intelligence, attention, and memory. The effect of a preexisting intracranial hemorrhage, as well as AVM occlusion, on cognitive functions was analyzed after 1 and 2 years. Results: No cognitive declines were observed during follow-up. Instead significant improvements occurred in intelligence (1 year, +6.1 IQ points; 2 years, +5.1 IQ points), memory (1 year, +18.3 percentile score; 2 years, +12.2 percentile score), and attention (1 year, +19 percentile score; 2 years, +18 percentile score). Patients without previous intracranial hemorrhage improved more than patients with intracranial hemorrhage, although this difference was not statistically significant. The role of AVM occlusion on cognitive function is not clear at present. Conclusion: Radiosurgery does not induce measurable deterioration of cognitive function in patients with cerebral AVMs.

which connects the temporal lobe with the prefrontal cortex; and (3) fornix, which connects the hippocampus with the hypothalamus. Furthermore, most previous studies investigating WM changes in schizophrenia have used voxel-based analysis, typically of a highly restricted WM skeleton (eg TBSS) or whole-tract mean values from tractography, thereby losing anatomical specificity. The goal of this investigation therefore, was to use sophisticated diffusion tensor imaging (DTI) tractometry analysis to examine along-tract microstructural differences in three major temporal lobe WM tracts in a family study of schizophrenia. Inclusion of both patients and family members allowed a better examination of genetic (familial) liability, as well as disease-related processes. Methods: Twenty-five patients with schizophrenia, 24 non-psychotic healthy relatives, and 27 community controls participated. DTI data were acquired (3T GE) along 60 gradient directions with b-value 1300 s/mm2 and corrected for motion and distortion using ExploreDTI. DTI parameters fractional anisotropy (FA) and mean and radial diffusivity (MD, RD) were estimated. A population-based FA-template was constructed, to which all parameter maps were registered. The aforementioned temporal lobe tracts were isolated using targeted tractography. The fornix was further subdivided into left/right anterior columns, body and left/right fimbriae. Parameter values for each subject were calculated at evenly distributed points along the length of the tract masks in template space. ANCOVA was used to investigate the main effect of group membership on mean tract values (between-subject factors: group, gender, covariate: age), whilst the group:position interaction term in a 2-way ANOVA was used to identify group differences at each point along each tract. Results: Both patients with schizophrenia and non-psychotic relatives demonstrated lower mean and radial diffusivity in their fornix compared to controls using age and gender as covariates. Tract profiles illustrated group differences along the entire length of the fornix rather than localized differences. No other significant differences were found between groups. Discussion: We found both schizophrenia patients and their biological relatives had differences in two indices associated with WM microstructure, compared to controls along the length of the fornix; however, in an unexpected direction. Possible reasons for this surprising finding could be a true biological difference, volumetric differences present between groups, or methodological issues associated with DTI analyses in typically sized schizophrenia study populations. Further investigation of the relationship between the DTI parameters, white matter volume and anatomical structures bordering the fornix will be presented to understand these findings. The results of this analysis may allow a better understanding of not only these results, but also other findings of fractional anisotropy changes in schizophrenia.

The objective is to assess the diagnostic accuracy and interobserver variability of multiphase 3D gadolinium-enhanced magnetic resonance angiography (3D-Gd-MRA) for assessment of abdominal and pelvic vascular disease.In 41 patients from two different institutions multiphase 3D-Gd-MRA of the aorta and pelvis was performed using an identical scanning protocol. In a single breath-hold three to four consecutive phases were acquired. Stenoses in the renal arteries, and aorta and pelvic arteries were independently evaluated by three readers and compared with digital subtraction angiography. Interobserver variability was compared by means of a kappa statistic.Accuracy for stenosis grading consistently ranged between 80% and 90% for all three readers in all vessel segments studied. Good interobserver agreement was found with kappa values exceeding 0.75. Vessel segments with delayed fill-in could be reliably detected on the multiple successive MRA phases. Overall, MRA was rated slightly superior to Digital Subtraction Angiography in terms of interobserver variability, diagnostic confidence and image quality.Multiphase MRA is a highly robust technique with reproducible accuracy for different observers and different institutions. It can therefore be recommended for screening of atherosclerotic abdominal and pelvic disease.

Rationale and objectives To evaluate the diagnostic potential of fluid-attenuated inversion-recovery (FLAIR) MRI in the assessment of patients with cerebral arteriovenous malformations (AVMs) and to correlate the MR findings with clinical symptoms, in particular, perilesional gliosis and ischemic changes. Methods Forty-five patients with cerebral AVMs were examined with FLAIR and conventional T1- and T2-weighted MRI by using identical slice parameters. Images were assessed in a two-reader study for detection and delineation of gliotic and ischemic tissue. Also, the extent of the flow void phenomenon and image artifacts were evaluated. Results FLAIR MRI was rated superior to the conventional T2-weighted fast spin-echo imaging in the assessment of intralesional and perilesional gliosis. The superior delineation was a result of the suppression of cerebrospinal fluid, mild T1 weighting, and the more pronounced flow void phenomenon. There was no significant correlation between the extent of gliosis and the clinical symptoms. However, larger AVMs had more extensive signal changes. Conclusions FLAIR is a valuable MRI technique to assess gliotic and ischemic changes in or close to cerebral AVMs. Because gliotic and ischemic changes are common findings and are known to be associated with epilepsy, in the assessment of these patients FLAIR is clinically useful and may guide decisions about treatment-for instance, the extent of surgical resection of the potential epileptogenic focus.

New tumor-conformal radiation-treatment modalities have been established with the intention to spare normal tissue while maintaining or improving local tumor control. To document radiation-induced changes in normal brain and low-grade astrocytoma we measured regional cerebral blood volumes (rCBV) using a dynamic susceptibility-weighted contrast-enhanced MR technique (DSC-MRI). We attempted to assess pretherapeutic rCBV values and time- and dose-dependent changes following radiotherapy.For prospective and longitudinal assessment of rCBV in normal brain and low-grade astrocytoma, 25 patients with histologically proven fibrillary astrocytoma (WHO Grade II) were examined before radiotherapy and during follow-up. Based on CT- and MR-data sets in a stereotactic setup, three-dimensional (3D) treatment planning was done. Radiotherapy was delivered using fractionated stereotactic radiotherapy (FSRT) to mean and median total doses of 60.9 and 60 Gy, respectively (range, 55.8-66 Gy). During MR imaging for treatment planning and follow-up examinations, 55 T2-weighted gradient echo images were acquired before, during, and after intravenous contrast bolus injection. The acquired signal-time curves were converted into concentration-time curves. The area under the tissue concentration-time curve was calculated and normalized to an integrated arterial input function. Thus, absolute rCBV values could be calculated.Pretherapeutic mean rCBV for normal gray (GM) and white brain matter (WM) were 7.2 +/- 2.7 and 3.6 +/- 1.5 mL/100 g tissue, respectively. Mean rCBV for astrocytoma was 6.5 +/- 3.7 mL/100 g tissue. After radiotherapy, rCBV for GM and WM was significantly reduced (p0.01) in high-dose areas (40-100% of total dose). A nonsignificant reduction was measured in low-dose areas (up to 40% of total dose). Reduction of rCBV in astrocytomas to a plateau level of 4.6 +/- 0.4 mL/100 g tissue was measured at 6 months after radiotherapy and remained stable in locally controlled tumors.Monitoring of rCBV changes in normal brain and low-grade astrocytoma was feasible using a DSC-MRI technique. The method was able to document radiation effects in low-grade astrocytoma, even if the majority of tumors showed no change in diagnostic MR-imaging. Radiation induced decrease of rCBV in GM and WM was correlated to total dose delivered to a tissue area, with high doses causing a significant decrease. Minor decline of rCBV in GM and WM outside high-dose areas after stereotactic radiotherapy confirms the efficacy to spare normal brain tissue by the use of modern conformal radiotherapy techniques. Nonetheless, a critical minimal dose initiating rCBV changes is yet unknown.

Contrast-enhanced fluid-attentuated inversion recovery (FLAIR) magnetic resonance (MR) imaging has shown to be a valuable diagnostic modality in the assessment of cerebral gliomas. In this study we report of a potential pitfall regarding the delineation of enhancing tumor parts on contrast enhanced FLAIR imaging. In a limited number of patients, the administration of gadolinium obscures the area of contrast enhancement on contrast enhanced FLAIR images. Therefore the delineation of the macroscopic tumor parts, which are of great importance for the treatment planning is substantially worsened.