Development and Evaluation of an MRI Artifact-Free Aneurysm Clip.

BACKGROUND AND OBJECTIVES: The digital subtraction angiography is still the gold standard in the follow-up after aneurysm surgery, although it remains a repeating invasive technique with accumulating X-ray exposure. An alternative magnetic resonance angiography has the disadvantage of metal-related artifacts. A metal-free aneurysm clip could overcome this problem. Recent advances in manufacturing technologies of fiber-reinforced plastics might allow developing a prototype of a metal-free clip. METHODS: The prototype was formed out of carbon fiber-reinforced polyetheretherketone (CF-PEEK) in accordance with the standard clip design. In vivo and in vitro studies were performed to analyze the central nervous system biocompatibility. The prototype was tested in a phantom in a 3 T MRI scanner and microtomography scanner. For in vivo assessment, the left renal artery of rats was either ligated with a suture, clipped with a regular titanium clip or with the CF-PEEK prototype clip. The animals underwent standard MRI sequences and magnetic resonance angiography and assessment by a blinded neuroradiologist. RESULTS: Phantom studies showed no signs of artifacts. The prototype showed a reliable clamping and reopening after clip application, although the clamping force was reduced. In vivo studies showed a successful occlusion of the renal artery in all cases in the magnetic resonance angiography. Clip artifacts were statistically significant reduced in the prototype group (P < .01). CF-PEEK showed no signs of impaired biocompatibility compared with the titanium samples in vitro and in vivo. CONCLUSION: Former attempts of metal-free aneurysm clips did not meet the criteria of the standard clip design. In this study, the practicability of this new CF-PEEK artifact-free aneurysm clip has been proven. The further fabrication developments should overcome the problem of a reduced clamping force in the future. After clinical approval, it will improve the magnetic resonance image quality and might help to reduce the amount of digital subtraction angiography in the follow-up.

Impact of cannabis use on brain metabolism using 31P and 1H magnetic resonance spectroscopy.

PURPOSE: This prospective cross-sectional study investigated the influence of regular cannabis use on brain metabolism in young cannabis users by using combined proton and phosphorus magnetic resonance spectroscopy. METHODS: The study was performed in 45 young cannabis users aged 18-30, who had been using cannabis on a regular basis over a period of at least 2 years and in 47 age-matched controls. We acquired 31P MRS data in different brain regions at 3T with a double-resonant 1H/31P head coil, anatomic images, and 1H MRS data with a standard 20-channel 1H head coil. Absolute concentration values of proton metabolites were obtained via calibration from tissue water as an internal reference, whereas a standard solution of 75 mmol/l KH2PO4 was used as an external reference for the calibration of phosphorus signals. RESULTS: We found an overall but not statistically significant lower concentration level of several proton and phosphorus metabolites in cannabis users compared to non-users. In particular, energy-related phosphates such as adenosine triphosphate (ATP) and inorganic phosphate (Pi) were reduced in all regions under investigation. Phosphocreatine (PCr) showed lowered values mainly in the left basal ganglia and the left frontal white matter. CONCLUSION: The results suggest that the increased risk of functional brain disorders observed in long-term cannabis users could be caused by an impairment of the energy metabolism of the brain, but this needs to be verified in future studies.

Cranial MRI in Childhood Acute Leukemia during Treatment and Follow-Up Including the Impact of Intrathecal MTX-A Single-Center Study and Review of the Literature.

Due to high survival rates, long-term sequelae, especially neurotoxicity, need to be considered in childhood acute leukemias. In this retrospective analysis of morphologic changes of the brain in children treated for acute leukemias, we included 94 patients (77 ALL, 17 AML; 51 male, 43 female; median age: 5 years) from a single center. We analyzed 170 cranial MRI scans (T2, FLAIR axial) for morphologic alterations of the brain and variations of the ventricular width (GDAH). In addition, the corresponding literature was reviewed. More than 50% of all patients showed cerebral pathomorphologies (CP). They were seen more often in children with ALL (55.8%), ≤ 6 years of age (60.8%), in relapse (58.8%) or after CNS irradiation (75.0%) and included white matter changes, brain atrophy, sinus vein thrombosis and ischemic events. GDAH significantly enlarged mainly in children up to 6 years, with relapse, high-risk leukemias or ALL patients. However, GDAH can normalize again. The number of intrathecal Methotrexate applications (≤12 vs. >12) showed no correlation to morphologic alterations besides a significant increase in GDAH (−0.3 vs. 0.9 mm) between the first and last follow-up MRI in ALL patients receiving >12 ith. MTX applications. The role of ith. MTX on CP needs to be further investigated and correlated to the neurocognitive outcome of children with acute leukemias.

Gastric Motility in Parkinson's Disease is Altered Depending on the Digestive Phase and Does Not Correlate with Patient-Reported Motor Fluctuations.

BACKGROUND: Altered gastric motility is a frequent non-motor symptom of Parkinson's disease (PD). It has been hypothesized that disturbed gastric motility contributes to motor fluctuations in PD due to an erratic gastro-duodenal transport and an unpredictable absorption of drugs. OBJECTIVE: We investigated whether patient-reported fluctuations are associated with parameters of gastric motility visualized by real-time magnetic resonance imaging (MRI) of the stomach. METHODS: We analyzed real-time MRI-scans of the stomach after an overnight fasting period in 16 PD patients and 20 controls. MRI was performed 1) in the fasting state, 2) directly after a test meal, and 3) 4 hours postprandially. Gastric motility indices were calculated and compared between groups. RESULTS: MRI showed an attenuated gastric motility in PD patients compared to controls. The difference was most obvious in the early postprandial phase. Gastric motility was not associated with patient-reported motor fluctuations. Using an iron-containing capsule we were able to retrace retention of drugs in the stomach. CONCLUSION: The results of this study stress the importance of considering the phase of digestion when investigating gastric motility in PD. Despite theoretical considerations, we did not find robust evidence for an association between MRI parameters of gastric motility and patient-reported motor fluctuations. For future studies that aim to investigate gastric motility in PD by MRI, we suggest multiple short-time MRIs to better track the whole gastro-duodenal phase in PD. Such an approach would also allow to retrace the retention of drugs in the stomach as shown by our approach using an iron-containing capsule.

Normal brain aging and Alzheimer's disease are associated with lower cerebral pH: an in vivo histidine 1H-MR spectroscopy study.

It is unclear whether alterations in cerebral pH underlie Alzheimer's disease (AD) and other dementias. We performed proton spectroscopy after oral administration of histidine in healthy young and elderly persons and in patients with mild cognitive impairment and dementia (total N = 147). We measured cerebral tissue pH and ratios of common brain metabolites in relation to phosphocreatine and creatine (Cr) in spectra acquired from the hippocampus, the white matter (WM) of the centrum semiovale, and the cerebellum. Hippocampal pH was inversely associated with age in healthy participants but did not differ between patients and controls. WM pH was low in AD and, to a lesser extent, mild cognitive impairment but not in frontotemporal dementia spectrum disorders and pure vascular dementia. Furthermore, WM pH provided incremental diagnostic value in addition to N-acetylaspartate to Cr ratio. Our study suggests that in vivo assessment of pH may be a useful marker for the differentiation between AD and other types of dementia.

Basic Principles and Clinical Applications of Magnetic Resonance Spectroscopy in Neuroradiology.

Magnetic resonance spectroscopy is a powerful tool to assist daily clinical diagnostics. This review is intended to give an overview on basic principles of the technology, discuss some of its technical aspects, and present typical applications in daily clinical routine in neuroradiology.

Hippocampal integrity and neurocognition in first-episode schizophrenia: a multidimensional study.

OBJECTIVES: Impairments in memory and executive function are key components of schizophrenia. These disturbances have been linked to several subcortical and cortical networks. For example, anatomical and functional changes in the hippocampus have been linked to deficits in these cognitive domains. However, the association between hippocampal morphometry, neurochemistry and function is controversial. Therefore, we aimed to investigate the relationship between hippocampal anomalies and their functional relevance. METHODS: Fifty-seven first-episode schizophrenia patients (FE-SZ) and 61 healthy control subjects (HC) participated in this study. Hippocampal volumes were investigated using structural magnetic resonance imaging (sMRI) and hippocampal neurochemistry was determined using proton magnetic resonance spectroscopy (1H MRS). Verbal memory was used as a hippocampus-dependent cognitive task whereas working memory and cognitive flexibility assessed frontal lobe function. RESULTS: FE-SZ presented smaller volumes of the left hippocampus, with a significant correlation between left hippocampal volume and verbal memory performance (immediate recall). There was also an inverse correlation between neurochemical ratios (NAA/Cho and Cho/Cr) and verbal memory (delayed recognition). Tests of cognitive flexibility and working memory were not correlated with MRI and 1H MRS values. Compared to HC, FE-SZ demonstrated reduced performance in all of the assessed neurocognitive domains. CONCLUSIONS: These results point to a relationship between verbal memory and hippocampal integrity in schizophrenia patients which might be independent from deficits in other memory domains. Disturbed verbal memory functions in FE-SZ might be linked specifically to hippocampal function.

Association of the brain-derived neurotrophic factor val66met polymorphism with magnetic resonance spectroscopic markers in the human hippocampus: in vivo evidence for effects on the glutamate system.

The brain-derived neurotrophic factor (BDNF) is a key regulator of synaptic plasticity and has been suggested to be involved in the pathophysiology and pathogenesis of psychotic disorders, with particular emphasis on dysfunctions of the hippocampus. The aim of the present study was to replicate and to extend prior findings of BDNF val66met genotype effects on hippocampal volume and N-acetyl aspartate (NAA) levels. Hundred and fifty-eight caucasians (66 schizophrenic, 45 bipolar, and 47 healthy subjects; 105 subjects underwent MRI and 103 MRS scanning) participated in the study and were genotyped with regard to the val66met polymorphism (rs6265) of the BDNF gene. Hippocampal volumes were determined using structural magnetic resonance imaging (MRI), and measures of biochemical markers were taken using proton magnetic resonance spectroscopy ((1)H-MRS) in the hippocampus and other brain regions. Verbal memory was assessed as a behavioral index of hippocampal function. BDNF genotype did not impact hippocampal volumes. Significant genotype effects were found on metabolic markers specifically in the left hippocampus. In particular, homozygous carriers of the met-allele exhibited significantly lower NAA/Cre and (Glu + Gln)/Cre metabolic ratios compared with val/val homozygotes, independently of psychiatric diagnoses. BDNF genotype had a numerical, but nonsignificant effect on verbal memory performance. These findings provide first in vivo evidence for an effect of the functional BDNF val66met polymorphism on the glutamate system in human hippocampus.

Hippocampal plasticity in response to exercise in schizophrenia.

CONTEXT: Hippocampal volume is lower than expected in patients with schizophrenia; however, whether this represents a fixed deficit is uncertain. Exercise is a stimulus to hippocampal plasticity. OBJECTIVE: To determine whether hippocampal volume would increase with exercise in humans and whether this effect would be related to improved aerobic fitness. DESIGN: Randomized controlled study. SETTING: Patients attending a day hospital program or an outpatient clinic. PATIENTS OR OTHER PARTICIPANTS: Male patients with chronic schizophrenia and matched healthy subjects. INTERVENTIONS: Aerobic exercise training (cycling) and playing table football (control group) for a period of 3 months. MAIN OUTCOME MEASURES: Magnetic resonance imaging of the hippocampus. Secondary outcome measures were magnetic resonance spectroscopy, neuropsychological (Rey Auditory Verbal Learning Test, Corsi block-tapping test), and clinical (Positive and Negative Syndrome Scale) features. RESULTS: Following exercise training, relative hippocampal volume increased significantly in patients (12%) and healthy subjects (16%), with no change in the nonexercise group of patients (-1%). Changes in hippocampal volume in the exercise group were correlated with improvements in aerobic fitness measured by change in maximum oxygen consumption (r = 0.71; P = .003). In the schizophrenia exercise group (but not the controls), change in hippocampal volume was associated with a 35% increase in the N-acetylaspartate to creatine ratio in the hippocampus. Finally, improvement in test scores for short-term memory in the combined exercise and nonexercise schizophrenia group was correlated with change in hippocampal volume (r = 0.51; P < .05). CONCLUSION: These results indicate that in both healthy subjects and patients with schizophrenia hippocampal volume is plastic in response to aerobic exercise.

Influence of carotid artery stenting on cognitive function.

INTRODUCTION: There have only been a few studies on cognitive changes in patients with carotid occlusive disease, and the results of these show major discrepancies in the extent to which treatment affects neuropsychological function. We sought to clarify these discrepancies by evaluating the effects of carotid artery stenting (CAS) on the cognitive function. METHODS: Forty-one asymptomatic CAS patients were administered a test battery of neuropsychological tests measuring cognitive speed and memory function before and 3 months after the procedure. A control group was also evaluated. To test for thromboembolic lesions, diffusion-weighted imaging was used. RESULTS: CAS led to a significant increase in cognitive speed (p<0.001) but did not afford any change in memory function. This was regardless of the degree or side of stenosis or patient age or gender. CONCLUSION: CAS significantly improved functions that involve cognitive speed. Earlier studies did not differentiate between speed and memory tests and thus might have missed these changes. Further studies correlating changes in brain perfusion with increase in cognitive speed are needed.

Cortical neurochemistry in euthymic patients with bipolar I disorder.

OBJECTIVE: Prefrontal and anterior cingulate cortical regions are assumed to be involved in the pathophysiology of mood regulation. Reduced prefrontal and anterior cingulate function indicated by decreased N-acetyl-aspartate (NAA) levels in patients with bipolar disorder has been reported inconsistently. A positive correlation between lithium serum level and NAA concentrations has been found previously. The aim of this study was to re-investigate prefrontal and anterior cingulate neurochemistry in a sample of euthymic patients with bipolar I disorder. METHODS: NAA, choline (Cho), creatine (Cr) and myo-inositol (Ins) in left dorsolateral prefrontal cortex and left anterior cingulate cortex were measured in 33 euthymic patients with bipolar I disorder and 29 healthy comparison subjects by using proton magnetic resonance spectroscopy ([(1)H]MRS). RESULTS: Metabolic ratios did not differ between patients with bipolar I disorder and comparison subjects in prefrontal and anterior cingulate cortex neither in the total sample nor in the pairwise matched sub-sample. We could not observe an association between lithium level and NAA ratios. Lithium treated patients demonstrated unchanged NAA or myo-inositol ratios compared to alternatively treated patients. CONCLUSION: In contrast to prior findings, we could not observe any metabolic alterations in euthymic patients with bipolar disorder.

Dopamine transporter genotype influences N-acetyl-aspartate in the left putamen.

INTRODUCTION: Dopaminergic activity in the brain is modulated by the dopamine transporter (DAT). Several lines of evidence suggest that a variable number of tandem repeats (VNTR) polymorphism of the DAT1 gene (SLC6A3) influences its gene expression. The aim of this study was to determine whether the DAT1VNTR polymorphism alters the metabolic ratios NAA/Cho, NAA/Cr, Cho/Cr and Ins/Cr in the left dorsolateral prefrontal cortex, anterior cingulate cortex, and putamen in healthy subjects and psychiatric patients irrespective of clinical diagnosis. MATERIAL AND METHODS: Sixty-four individuals (30 patients with bipolar disorder, 18 patients with obsessive-compulsive disorder, and 16 healthy subjects) participated in the study. The 3'-UTR VNTR polymorphism of DAT1 (SLC6A3) gene was genotyped in all individuals. (1)H-MRS was performed in the above-mentioned brain regions. RESULTS: The individuals with the homozygous DAT1 10-repeat genotype presented significantly higher ratios of NAA/Cho and NAA/Cr in the left putamen compared to the group of individuals with the 9/9-repeat or 9/10-repeat genotype. CONCLUSION: The VNTR polymorphism of the DAT1-gene modulates NAA/Cho and NAA/Cr in the left putamen independent of psychiatric diagnosis status. These results suggest an association of DAT1 VNTR polymorphism, dopaminergic activity, and neuronal function in putamen.

SNAP-25 genotype influences NAA/Cho in left hippocampus.

The SNAP-25 gene is an integral part of the vesicle docking and fusion machinery that controls neurotransmitter release. Several post mortem studies revealed a reduction of SNAP-25 protein in the hippocampus of patients with schizophrenia and bipolar disorder (BD). Thirty-eight patients with schizophrenia, BD or obsessive-compulsive disorder and 17 healthy controls participated in the study. Proton magnetic resonance spectroscopy in left hippocampus was performed in each individual. Three single nucleotide polymorphisms (SNP) of the SNAP-25 gene were genotyped. Individuals with the homozygous CC genotype of the DdeI SNP presented a significantly higher ratio of N-acetyl-aspartate (NAA)/choline-containing compounds (Cho) in the left hippocampus compared to the group of individuals with the homozygous TT genotype. The SNAP-25 genotype may modulate synaptic plasticity and neurogenesis in the left hippocampus, and altered NAA/Cho ratio may be an indicator for this genetic modulation of neuronal function in the hippocampus.

MRI of the brainstem in patients with major depression, bipolar affective disorder and normal controls.

Structural imaging studies of bipolar affective disorder or major depression have shown a spectrum of abnormal findings. However, a characteristic pattern of abnormality for either disease has not yet emerged. While the majority of studies focused on brain atrophy and the volumes of supratentorial cerebral structures, little attention has been paid to infratentorial structures. This MRI study focused on the pontomesencephalic area including the region of the raphe nuclei. The raphe nuclei are of special interest in affective disorders as they are the origin of the major serotonergic projections in this region. MRI scans of 10 bipolar I patients, 10 patients with major depression and 10 age-matched healthy control subjects were studied. The brain stem and the fourth ventricle areas as well as T2-relaxation times in the area of the raphe nuclei were evaluated. A difference between patients with major depression and control subjects for T(2)-relaxation times was found in a region of interest located along the midline of the pons. No difference was found between patients with bipolar disorder and control subjects. This finding needs to be replicated in a larger sample with more elaborated MRI techniques (multi-echo sequences) for the determination of T2-relaxation times.

Monocular visual activation patterns in albinism as revealed by functional magnetic resonance imaging.

Human albinism is characterized by a disturbance of the chiasmatic projection system leading to predominant representation of just one eye in the contralateral hemisphere. Patients show congenital nystagmus without perceiving oscillopsia. The purpose of the present study was to demonstrate the consequences of atypical chiasmatic crossing with monocular visual stimulation using functional magnetic resonance imaging (fMRI). Sixteen patients with albinism and fifteen normally pigmented controls were stimulated with a monocular visual activation paradigm using flickering checkerboards. In patients, we observed contralaterally dominated activation of visual cortices correlating to clinical albinism parameters. This confirms albinism as a continuous range of hypopigmentation disorders. Additionally, albinos showed activation of the superior colliculus and of visual motion areas although the stimulus was stationary. Activation of visual motion areas is due probably to congenital nystagmus without a conscious correlate like oscillopsia.

Transient dystonia following magnetic resonance imaging in a patient with deep brain stimulation electrodes for the treatment of Parkinson disease. Case report.

Data from previous studies have shown that magnetic resonance (MR) imaging of the head can be performed safely in patients with deep brain stimulators. The authors report on a 73-year-old patient with bilaterally implanted deep brain electrodes for the treatment of Parkinson disease, who exhibited dystonic and partially ballistic movements of the left leg immediately after an MR imaging session. Such dystonic or ballistic movements had not been previously observed in this patient. In the following months, this focal movement disorder resolved completely. This case demonstrates the possible risks of MR imaging in patients with deep brain stimulators.

Configuration of the optic chiasm in humans with albinism as revealed by magnetic resonance imaging.

PURPOSE: To determine whether the size and configuration of the optic chiasm in humans with albinism is different from that in normal control subjects. METHODS: Seventeen patients and 15 control subjects underwent magnetic resonance imaging of the entire head. Images were reformatted to the chiasm region and analyzed with observer-independent morphometry and measurements by a blinded observer. RESULTS: The albino group showed significantly smaller chiasmatic widths, smaller optic nerves and tracts, and wider angles between nerves and tracts. Statistical morphometry showed a different configuration of the optic chiasm. CONCLUSIONS: Size and configuration of the optic chiasm in humans with albinism are distinctly different from those in normal control subjects and reflect the atypical crossing of optic fibers.