PubMed Health⌕ Search

Biomedical subjects

Martin Bendszus

Publications and source records attributed to Martin Bendszus.

At least 19 recordsLinked to original sources
PubMed2007

Manifestations of early brain recovery associated with abstinence from alcoholism.

Chronic alcohol abuse results in morphological, metabolic, and functional brain damage which may, to some extent, be reversible with early effects upon abstinence. Although morphometric, spectroscopic, and neuropsychological indicators of cerebral regeneration have been described previously, the overall amount and spatial preference of early brain recovery attained by abstinence and its associations with other indicators of regeneration are not well established. We investigated global and local brain volume changes in a longitudinal two-timepoint study with T1-weighted MRI at admission and after short-term (6-7 weeks) sobriety follow-up in 15 uncomplicated, recently detoxified alcoholics. Volumetric brain gain was related to metabolic and neuropsychological recovery. On admission and after short-term abstinence, structural image evaluation using normalization of atrophy (SIENA), its voxelwise statistical extension to multiple subjects, proton MR spectroscopy (1H-MRS), and neuropsychological tests were applied. Upon short-term sobriety, 1H-MRS levels of cerebellar choline and frontomesial N-acetylaspartate (NAA) were significantly augmented. Automatically detected global brain volume gain amounted to nearly two per cent on average and was spatially significant around the superior vermis, perimesencephalic, periventricular and frontal brain edges. It correlated positively with the percentages of cerebellar and frontomesial choline increase, as detected by 1H-MRS. Moreover, frontomesial NAA gains were associated with improved performance on the d2-test of attention. In 10 age- and gender-matched healthy control subjects, no significant brain volume or metabolite changes were observed. Although cerebral osmotic regulations may occur initially upon sobriety, significant increases of cerebellar choline and frontomesial NAA levels detected at stable brain water integrals and creatine concentrations, serum electrolytes and red blood cell indices in our patient sample suggest that early brain recovery through abstinence does not simply reflect rehydration. Instead, even the adult human brain and particularly its white matter seems to possess genuine capabilities for regrowth. Our findings emphasize metabolic as well as regionally distinct morphological capacities for partial brain recovery from toxic insults of chronic alcoholism and substantiate early measurable benefits of therapeutic sobriety. Further understanding of the precise mechanisms of this recovery may become a valuable model of brain regeneration with relevance for other disorders.

Adult↗
PubMed2006

Scanning for the scanner: FMRI of audition by read-out omissions from echo-planar imaging.

Echo-planar imaging (EPI) generates considerable acoustic noise by rapidly oscillating gradients. In functional magnetic resonance imaging (FMRI), unshielded EPI sounds activate the auditory system inasmuch as it is responsive. Instead of attenuating EPI noise, our goal was to utilize it for auditory FMRI by omitting read-outs from the pulse sequence's gradient train. Read-out gradient pulses are the primary noise determinant of EPI introducing its peak sound level and fundamental frequency peak which inversely relates to twice the echo spacing. Using model-driven analyses, we demonstrate that withholding read-outs from EPI is suited to reliably evoke hemodynamic blood oxygenation level-dependent (BOLD) signal modulations bilaterally in the auditory cortex of normal hearing subjects (n=60). To investigate the utility of EPI read-out omissions for auditory FMRI at an individual subject's level, we compare traditional Family-Wise-Error-Rate (FWER)-corrected maximum height thresholding to spatial mixture modeling (SMM). With the latter, appropriate bilateral auditory activations were confirmed in 95% of the individuals, whereas FWER-based voxel thresholding detected such activations in up to 72%. We illustrate the applicability of this novel EPI modification for clinical diagnostic purposes and report on a patient with bilateral large vestibular aqueducts (LVAs) and severe binaural sensorineural hearing loss (SNHL). In this particular case, read-out omissions from EPI were used to assert residual audition prior to cochlear implantation (CI). Requiring no specific task compliance or sophisticated stimulation equipment other than the scanner on its own, FMRI by read-out omissions lends itself to auditory investigations and to quickly probe audition.

Acoustic Stimulation↗
PubMed2006

In vivo visualization of focal demyelination in peripheral nerves by gadofluorine M-enhanced magnetic resonance imaging.

Magnetic resonance imaging (MRI) allows assessment of axonal nerve lesions, but detection of focal demyelination is still difficult. We have recently shown that the novel micellar magnetic resonance (MR) contrast agent gadofluorine M (Gf) accumulates in nerve fibers undergoing Wallerian degeneration. In the present study, we report on the in vivo visualization of focal demyelination induced by lysolecithin. Upon appropriate intraneural injection, lysolecithin focally dissolves myelin sheaths with sparing of axons. Conventional unenhanced and gadolinium-DTPA enhanced T1-w MRI did not show signal alterations or contrast enhancement. In contrast, application of Gf led to bright contrast enhancement on T1-w images at the site of focal demyelination, but spared distal nerve segments not affected by demyelination. Gf enhancement persisted until remyelination had occurred. Our study shows that areas of focal nerve demyelination can be detected in vivo by Gf-enhanced MRI. This finding opens up a broad spectrum of applications in experimental neurology, and, depending on further clinical development of Gf, may aid in the diagnostic work up of patients with patchy, multifocal demyelinative disorders in the future.

Animals↗
PubMed2006

Immune cells contribute to myelin degeneration and axonopathic changes in mice overexpressing proteolipid protein in oligodendrocytes.

Overexpression of the major myelin protein of the CNS, proteolipid protein (PLP), leads to late-onset degeneration of myelin and pathological changes in axons. Based on the observation that in white matter tracts of these mutants both CD8+ T-lymphocytes and CD11b+ macrophage-like cells are numerically elevated, we tested the hypothesis that these cells are pathologically involved in the primarily genetically caused neuropathy. Using flow cytometry of mutant brains, CD8+ cells could be identified as activated effector cells, and confocal microscopy revealed a close association of the T-cells with MHC-I+ (major histocompatibility complex class I positive) oligodendrocytes. Crossbreeding the myelin mutants with mice deficient in the recombination activating gene-1 (RAG-1) lacking mature T- and B-lymphocytes led to a reduction of the number of CD11b+ cells and to a substantial alleviation of pathological changes. In accordance with these findings, magnetic resonance imaging revealed less ventricular enlargement in the double mutants, partially because of more preserved corpora callosa. To investigate the role of CD8+ versus CD4+ T-lymphocytes, we reconstituted the myelin-RAG-1 double mutants with bone marrow from either CD8-negative (CD4+) or CD4-negative (CD8+) mice. The severe ventricular enlargement was only found when the double mutants were reconstituted with bone marrow from CD8+ mice, suggesting that the CD8+ lymphocytes play a critical role in the immune-related component of myelin degeneration in the mutants. These findings provide strong evidence that a primary glial damage can cause secondary immune reactions of pathological significance as it has been suggested for some forms of multiple sclerosis and other leukodystrophies.

Animals↗
PubMed2006

Inflammation and atherosclerosis: novel insights into plaque formation and destabilization.

BACKGROUND AND PURPOSE: The simplistic view of atherosclerosis as a disorder of pathological lipid deposition has been redefined by the more complex concept of an ongoing inflammatory response. SUMMARY OF REVIEW: Apolipoprotein E and low-density lipoprotein (LDL)-receptor-deficient mice develop accelerated atherosclerosis allowing in-depth pathophysiological investigations. Atherosclerotic plaques in these mice contain large numbers of T cells and macrophages. Crossbreeding apolipoprotein E-deficient mice with T-cell-deficient mice and mice with impaired macrophage function (osteopetrotic op/op mice) disclosed the important impact of immune cells on atherosclerotic lesion development. In contrast to the detrimental role of T cells and macrophages, B cells appear to be atheroprotective. These basic experimental findings have partly been confirmed in studies of the human carotid artery system. Inflammation is not only instrumental in the development of human atheromatous plaques, but, importantly, plays a crucial role in the destabilization of internal carotid artery plaques, thus converting chronic atherosclerosis into an acute thrombo-embolic disorder. Humoral factors involved in internal carotid artery destabilization include cytokines, cyclooxygenase-2, matrix metalloproteinases, and tissue factor. Antibodies to oxidized LDL can reflect disease activity on one hand, but can also confer atheroprotection. Novel MRI techniques may aid in the in vivo assessment of acute plaque inflammation in humans. CONCLUSIONS: The impact of inflammation on the development of atherosclerotic plaques and their destabilization opens new avenues for treatment. The effects of statins, acetylsalicyclic acid and angiotensin-converting enzyme inhibitors on stroke prevention may partly be attributable to their profound anti-inflammatory actions. Vaccination against modified LDL and heat shock proteins halt plaque progression in experimental atherosclerosis. Their potential for prevention of human atherosclerosis is currently under investigation.

Animals↗
PubMed2006

Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis.

Formation of fibrin is critical for limiting blood loss at a site of blood vessel injury (hemostasis), but may also contribute to vascular thrombosis. Hereditary deficiency of factor XII (FXII), the protease that triggers the intrinsic pathway of coagulation in vitro, is not associated with spontaneous or excessive injury-related bleeding, indicating FXII is not required for hemostasis. We demonstrate that deficiency or inhibition of FXII protects mice from ischemic brain injury. After transient middle cerebral artery occlusion, the volume of infarcted brain in FXII-deficient and FXII inhibitor-treated mice was substantially less than in wild-type controls, without an increase in infarct-associated hemorrhage. Targeting FXII reduced fibrin formation in ischemic vessels, and reconstitution of FXII-deficient mice with human FXII restored fibrin deposition. Mice deficient in the FXII substrate factor XI were similarly protected from vessel-occluding fibrin formation, suggesting that FXII contributes to pathologic clotting through the intrinsic pathway. These data demonstrate that some processes involved in pathologic thrombus formation are distinct from those required for normal hemostasis. As FXII appears to be instrumental in pathologic fibrin formation but dispensable for hemostasis, FXII inhibition may offer a selective and safe strategy for preventing stroke and other thromboembolic diseases.

Animals↗
PubMed2006

Diagnostic functional MRI: illustrated clinical applications and decision-making.

Functional magnetic resonance imaging (fMRI) has become a popular research tool, yet its use for diagnostic purposes and actual treatment planning has remained less widespread. The literature yields rather sparse evidence-based data on clinical fMRI applications and accordant decision-making. Notwithstanding, blood oxygenation level dependent (BOLD)- and arterial spin labeling (ASL)-fMRI can be judiciously combined with perfusion measurements, electroencephalographic (EEG) recordings, diffusion-weighted imaging (DWI), and fiber tractographies to assist clinical decisions. In this article we provide an overview of clinical fMRI applications based on illustrative examples. Assessment of cochlear implant candidates by fMRI is covered in some detail, and distinct reference is made to particular challenges imposed by brain tumors, other space-occupying lesions, cortical dysplasias, seizure disorders, and vascular malformations. Specific strategies, merits, and pitfalls of analyzing and interpreting diagnostic fMRI studies in individual patients are highlighted.

Brain Diseases↗
PubMed2006

Denervation hypertrophy may mimic local tumor spread on magnetic resonance imaging.

We report a patient with an extensive paranasal sinus carcinoma. One year after tumor resection, magnetic resonance imaging (MRI) showed swelling of the ipsilateral masticatory muscles with signal increase on T2-weighted images and gadolinium-DTPA uptake, suggestive of local tumor infiltration. However, electromyography, biopsy, and follow-up MRI confirmed denervation pseudohypertrophy of the muscles innervated by the mandibular nerve and excluded tumor recurrence. Muscle denervation and pseudohypertrophy should be considered in the differential diagnosis of appropriate patients with suspected tumor recurrence.

Adult↗
PubMed2006

Silent cerebral ischaemia: hidden fingerprints of invasive medical procedures.

Cardiovascular and cerebrovascular disorders are the main cause of death and permanent disability worldwide. Improved diagnostic and therapeutic options for these diseases have led to increasing numbers of invasive procedures such as angiography, stent placement, and operations exceeding 4 million each year in the USA. Although clinical examinations suggest a relatively low risk for ischaemic complications affecting the brain, new magnetic resonance techniques have led to the awareness of much higher numbers of clinically silent ischaemic brain lesions. Diffusion-weighted MRI (DWI) has shown new ischaemic lesions in a substantial number of patients undergoing cardiac or carotid-artery surgery, and coronary or cerebral-angiographic interventions. The clinical impact of these "silent" ischaemic lesions within brain areas without primary motor, sensory, or linguistic function ("non-eloquent" brain areas) is debated. There is increasing evidence, however, that cumulative burden of ischaemic brain injury causes neuropsychological deficits or aggravates vascular dementia. Thus, DWI emerges as a valuable diagnostic method for the monitoring of periprocedural ischaemic events in the brain, and could be a surrogate parameter for optimising diagnostic and therapeutic vascular procedures in the future.

Brain↗
PubMed2005

Cytokine profile of iron-laden macrophages: implications for cellular magnetic resonance imaging.

Superparamagnetic iron oxide (SPIO/USPIO) particles are a promising new tool to label cells for in vivo monitoring of their migration into the nervous system by magnetic resonance imaging (MRI). Upon systemic application, SPIO/USPIO particles are preferentially internalized by macrophages. It is unclear whether this affects their immunological profile. We tested the cytokine production of rat and mouse macrophages in vitro and found that internalization of SPIO/USPIO shifted macrophages towards an anti-inflammatory, less responsive phenotype by enhancing interleukin (IL)-10 and inhibiting tumor necrosis factor (TNF)-alpha production. During macrophage interaction with T-cells IL-12p40 secretion was inhibited. Based on our in vitro findings, potential immunomodulatory effects of SPIO/USPIO particles in vivo warrant further investigation.

Animals↗
PubMed2005

In vivo molecular imaging of adhesion molecules in experimental autoimmune encephalomyelitis (EAE).

The infiltration of autoreactive T cells into the central nervous system (CNS) requires a complex molecular interplay between immune cells and the blood-brain barrier (BBB), especially involving adhesion molecules like intercellular adhesion molecule (ICAM)-1. Here we study the molecular expression at the BBB during adoptively transferred (AT) myelin basic protein (MBP)-experimental autoimmune encephalomyelitis (EAE) in vivo by sensitive particle acoustic quantification (SPAQ)-enhanced ultrasound after intravenous application of specific gas-filled MP (MP) targeted against ICAM-1 (ICAM-MP) as contrast agent. Our results reveal a clear periventricular and cerebellar upregulation of ICAM-1 expression at the disease maximum of AT-EAE. Moreover, SPAQ-enhanced ultrasound enables the sensitive quantification of ICAM-1 expression in vivo. This allows to monitor therapeutic changes as shown by suppression of ICAM-1 expression after pretreatment of rats with corticosteroids (P < 0.008). All imaging results were confirmed by parallel immunohistochemistry. In vivo magnetic resonance imaging and albumin staining of rat brains after sonification did not reveal a disturbance of the BBB, thereby proving the safety of the method. Subsequent application of specific MP did not influence follow-up measurements, a prerequisite for sequential measurements in longitudinal studies. Based on these data, quantitative molecular imaging of adhesion molecules by SPAQ-enhanced ultrasound proves to be a safe and reliable technology to monitor changes at the BBB in vivo.

Animals↗
PubMed2005

Assessment of lesion evolution in experimental autoimmune neuritis by gadofluorine M-enhanced MR neurography.

Experimental autoimmune neuritis (EAN) represents an animal model of acute inflammatory nerve injury mirroring pathophysiological aspects of the human Guillain-Barré syndrome. In the present study, we for the first time visualized the spatiotemporal evolution of autoimmune nerve injury and recovery by magnetic resonance imaging (MRI) by use of the novel micellar magnetic resonance (MR) contrast agent gadofluorine M (Gf). EAN was induced in Lewis rats by T-cell transfer (AT-EAN) leading to severe axonal damage, and Gf was applied intravenously at various disease stages mostly 24 h before MRI. In naive rats, Gf enhancement was present solely in the vascular compartment. In AT-EAN, clinically asymptomatic rats already showed consistent Gf uptake in spinal nerves on day 3, while sciatic nerves were spared. The cauda equina correspondingly exhibited massive T-cell infiltration. Gf enhancement further extended to the plexus lumbosacralis on day 4. On days 5 and 6, the entire peripheral neuraxis from the cauda equina, along the sciatic down to the tibial and peroneal nerves, showed strong Gf enhancement. Spinal and peripheral nerves now exhibited massive inflammation and axonal injury on parallel histological analysis. Gf enhancement persisted in the afflicted nerves until complete recovery and disappeared with a proximodistal gradient. In conclusion, Gf-enhanced MR neurography opens a new avenue for monitoring nerve damage in-vivo during an immune attack.

Animals↗
PubMed2005

Proximal stent fixation of fractured coils: technical note.

Coil fracture represents a serious device-related complication during coil embolisation of intracranial aneurysms. If the coil cannot be retrieved completely, the loose end floating in the parent vessel can prolapse into the distal part of the vessel and may cause occlusion and brain infarction. We present a new technique in which the loose end of the fractured coil is fixed with a stent at the proximal parent vessel wall. Herniation of the loose coil end to the distal part of the vessel with potential vessel occlusion is therefore prevented. This procedure was technically feasible in all cases and no clinical complications were encountered. We suggest this new technique as a treatment option in cases of fractured coils.

Cerebral Angiography↗
PubMed2005

Assessment of nerve degeneration by gadofluorine M-enhanced magnetic resonance imaging.

Nerve injury represents a major cause of disability. In the peripheral nervous system, nerves have the capacity to regrow but within weeks after injury, it is impossible to clarify whether proper regeneration is under way or is failing. In this experimental study, we report on a novel tool to assess nerve outgrowth in vivo. After systemic application, the novel gadolinium-based magnetic resonance (MR) contrast agent Gadofluorine M (Gf) selectively accumulated and persisted in nerve fibers undergoing Wallerian degeneration causing bright contrast on T1-weighted MR images. Gf enhancement on MR imaging was present already at 48 hours within the entire nerve segments undergoing Wallerian degeneration, and subsequently disappeared from proximal to distal parts in parallel to regrowth of nerve fibers. Most importantly, Gf enhancement persisted in nonregenerating, permanently transected nerves. Our novel Gf-based MR imaging methodology holds promise for clinical use to bridge the diagnostic gap between nerve injury and completed nerve regeneration, and to determine the necessity for neurolysis and engraftment if spontaneous regeneration is not successful.

Animals↗
PubMed2005

Technology insight: visualizing peripheral nerve injury using MRI.

Currently, the evaluation of peripheral nerve disorders depends on clinical examination, supplemented by electrophysiological studies. These approaches provide general information on the distribution and classification of nerve lesions-for example, axonal versus demyelinative-but nerve biopsies are still required to obtain morphological and pathophysiological details. In this article, we review recent progress in the imaging of peripheral nerve injury by magnetic resonance (MR) neurography. Axonal nerve injury leads to Wallerian degeneration, resulting in a hyperintense nerve signal on T2-weighted MR images of the distal nerve segment. This signal is lost following successful regeneration. Concomitant denervation-induced signal alterations in muscles can further help us to determine whether nerve trunks or roots are affected. These signal changes are caused by various combinations of nonspecific tissue alterations, however, and are not related to particular pathoanatomical findings, such as inflammation, demyelination or axonal injury. New experimental MR contrast agents, such as gadofluorine M and superparamagnetic iron oxide particles, allow visualization of the dynamics of peripheral nerve injury and repair. Further clinical development of these MR contrast agents should allow these functional aspects of nerve injury and repair to be assessed in humans, thereby aiding the differential diagnosis of peripheral nerve disorders.

Animals↗
PubMed2005

In vivo detection of developing vessel occlusion in photothrombotic ischemic brain lesions in the rat by iron particle enhanced MRI.

The aim of our study was to visualize developing vessel occlusion in focal cerebral ischemia in vivo. Cortical photothrombosis (PT) was induced in rats, which in addition received superparamagnetic iron oxide (SPIO) particles intravenously. When SPIO particles were applied simultaneously during illumination of the brain for induction of PT, animals showed a markedly hypointense cortical lesion on T2-weighted (T2-w) magnetic-resonance images (MRI). At 3 h after PT, this hypointense area was surrounded by a small hyperintense rim. At 48 h after PT the hyperintense rim had further extended, whereas the hypointense lesion core did not change in size or signal. On histological sections areas of signal loss on T2-w MRI corresponded to local accumulation of iron particles, which were trapped within vessel thrombi. When SPIO particles were applied at 2 h after PT, the lesion appeared hyperintense on T2-w MRI, but was surrounded by a small hypointense rim indicating ongoing vessel occlusion at its outer margins. In contrast, delayed SPIO application at 24 h after completion of PT produced a merely hyperintense cortical lesion on T2-w MRI. Correspondingly, no iron deposits were seen on tissue sections. In conclusion, early SPIO-enhanced MRI provides a reliable in vivo tool to delineate areas of developing vessel occlusion in experimental cerebral ischemia and identifies vessel thrombosis as one mechanism of secondary infarct growth in the PT paradigm. This new imaging technique may aid to evaluate antithrombotic treatment strategies in the future.

Animals↗