Back to the future: breast surgery with tumescent local anesthesia (TLA)?

PURPOSE: Breast surgery is usually performed under general anesthesia. Tumescent local anesthesia (TLA) offers the possibility to anesthetize large areas with highly diluted local anesthetic. METHODS: In this paper, the implementation, and experiences with TLA in the field of breast surgery are discussed. CONCLUSION: For carefully selected indications, breast surgery in TLA represents an alternative to ITN.

Non-negative least squares computation for in vivo myelin mapping using simulated multi-echo spin-echo T2 decay data.

Multi-compartment T2 mapping has gained particular relevance for the study of myelin water in the brain. As a facilitator of rapid saltatory axonal signal transmission, myelin is a cornerstone indicator of white matter development and function. Regularized non-negative least squares fitting of multi-echo T2 data has been widely employed for the computation of the myelin water fraction (MWF), and the obtained MWF maps have been histopathologically validated. MWF measurements depend upon the quality of the data acquisition, B1+ homogeneity and a range of fitting parameters. In this special issue article, we discuss the relevance of these factors for the accurate computation of multi-compartment T2 and MWF maps. We generated multi-echo spin-echo T2 decay curves following the Carr-Purcell-Meiboom-Gill approach for various myelin concentrations and myelin T2 scenarios by simulating the evolution of the magnetization vector between echoes based on the Bloch equations. We demonstrated that noise and imperfect refocusing flip angles yield systematic underestimations in MWF and intra-/extracellular water geometric mean T2 (gmT2 ). MWF estimates were more stable than myelin water gmT2 time across different settings of the T2 analysis. We observed that the lower limit of the T2 distribution grid should be slightly shorter than TE1 . Both TE1 and the acquisition echo spacing also have to be sufficiently short to capture the rapidly decaying myelin water T2 signal. Among all parameters of interest, the estimated MWF and intra-/extracellular water gmT2 differed by approximately 0.13-4 percentage points and 3-4 ms, respectively, from the true values, with larger deviations observed in the presence of greater B1+ inhomogeneities and at lower signal-to-noise ratio. Tailoring acquisition strategies may allow us to better characterize the T2 distribution, including the myelin water, in vivo.

Systematic analysis of parameters predicting pathological axillary status (ypN0 vs. ypN+) in patients with breast cancer converting from cN+ to ycN0 through primary systemic therapy (PST).

Optimization of axillary staging among patients converting from clinically node-positive disease to clinically node-negative disease through primary systemic therapy is needed. We aimed at developing a nomogram predicting the probability of positive axillary status after chemotherapy based on clinical/pathological parameters. Patients from study arm C of the SENTINA trial were included. Univariable/multivariable analyses were performed for 13 clinical/pathological parameters to predict a positive pathological axillary status after chemotherapy using logistic regression models. Odds ratios and 95%-confidence-intervals were reported. Model performance was assessed by leave-one-out cross-validation. Calculations were performed using the SAS Software (Version 9.4, SAS Institute Inc., Cary, NC, USA). 369 of 553 patients in Arm C were included in multivariable analysis. Stepwise backward variable selection based on a multivariable analysis resulted in a model including estrogen receptor (ER) status (odds ratio (OR) 3.916, 95% confidence interval (CI) 2.318-6.615, p < 0.001), multifocality (OR 2.106, 95% CI 1.203-3.689, p = 0.0092), lymphovascular invasion (OR 9.196, 95% CI 4.734-17.864, p < 0.001), and sonographic tumor diameter after PST (OR 1.034, 95% CI 1.010-1.059, p = 0.0051). When validated, our model demonstrated an accuracy of 70.2% using 0.5 as cut-point. An area under the curve of 0.81 was calculated. The use of individual parameters as predictors of lymph node status after chemotherapy resulted in an inferior accuracy. Our model was able to predict the probability of a positive axillary nodal status with a high accuracy. The use of individual parameters showed reduced predictive performance. Overall, tumor biology was the strongest parameter in our models.

High intensity focused ultrasound (HIFU) for the treatment of symptomatic breast fibroadenoma.

PURPOSE: The aim of the study was to evaluate the efficacy of high intensity focused ultrasound (HIFU) in the treatment of symptomatic breast fibroadenomas (FA) after 6 and 12 months. MATERIALS AND METHODS: Between December 2013 and November 2014, 27 patients with histologically confirmed FA received one application of HIFU under local anesthesia (NCT02011919). Follow-up visits occurred after 6 and 12 months measuring the FA volume and clinical symptoms. A volume reduction of more than 65% was defined as success. Core needle biopsy (CNB) was offered after 12 months if indistinct residuals were visible on ultrasound (US). RESULTS: A successful reduction in FA volume after 12 months was achieved in 24/27 patients (89%). At baseline 16 patients (59%) had pain, which was resolved in 63% (10/16). All patients were satisfied with the cosmetic related outcome. Twenty-four patients (89%) would repeat the procedure. After 12 months 21 patients with sonographically indistinct residuals underwent a CNB. There were no vital cells in 86%. Three cases showed vital cells of FA. Retrospectively possible reasons in these three cases were an insufficient treatment due to bad visibility and insufficient fixation of the FA during HIFU and/or a too short follow-up time. CONCLUSION: US-guided HIFU is an effective procedure and a minimally invasive alternative for the treatment of breast FA.

Biofilm adaptation to iron availability in the presence of biotite and consequences for chemical weathering.

Bacteria in nature often live within biofilms, exopolymeric matrices that provide a favorable environment that can differ markedly from their surroundings. Biofilms have been found growing on mineral surfaces and are expected to play a role in weathering those surfaces, but a clear understanding of how environmental factors, such as trace-nutrient limitation, influence this role is lacking. Here, we examine biofilm development by Pseudomonas putida in media either deficient or sufficient in Fe during growth on biotite, an Fe rich mineral, or on glass. We hypothesized that the bacteria would respond to Fe deficiency by enhancing biotite dissolution and by the formation of binding sites to inhibit Fe leaching from the system. Glass coupons acted as a no-Fe control to investigate whether biofilm response depended on the presence of Fe in the supporting solid. Biofilms grown on biotite, as compared to glass, had significantly greater biofilm biomass, specific numbers of viable cells (SNVC), and biofilm cation concentrations of K, Mg, and Fe, and these differences were greater when Fe was deficient in the medium. Scanning electron microscopy (SEM) confirmed that biofilm growth altered the biotite surface, smoothing the rough, jagged edges of channels scratched by hand on the biotite, and dissolving away small, easy-to-access particles scattered across the planar surface. High-resolution magic angle spinning proton nuclear magnetic resonance (HRMAS 1 H NMR) spectroscopy showed that, in the Fe-deficient medium, the relative amount of polysaccharide nearly doubled relative to that in biofilms grown in the medium amended with Fe. The results imply that the bacteria responded to the Fe deficiency by obtaining Fe from biotite and used the biofilm matrix to enhance weathering and as a sink for released cation nutrients. These results demonstrate one mechanism by which biofilms may help soil microbes overcome nutrient deficiencies in oligotrophic systems.

New tissue priors for improved automated classification of subcortical brain structures on MRI.

Despite the constant improvement of algorithms for automated brain tissue classification, the accurate delineation of subcortical structures using magnetic resonance images (MRI) data remains challenging. The main difficulties arise from the low gray-white matter contrast of iron rich areas in T1-weighted (T1w) MRI data and from the lack of adequate priors for basal ganglia and thalamus. The most recent attempts to obtain such priors were based on cohorts with limited size that included subjects in a narrow age range, failing to account for age-related gray-white matter contrast changes. Aiming to improve the anatomical plausibility of automated brain tissue classification from T1w data, we have created new tissue probability maps for subcortical gray matter regions. Supported by atlas-derived spatial information, raters manually labeled subcortical structures in a cohort of healthy subjects using magnetization transfer saturation and R2* MRI maps, which feature optimal gray-white matter contrast in these areas. After assessment of inter-rater variability, the new tissue priors were tested on T1w data within the framework of voxel-based morphometry. The automated detection of gray matter in subcortical areas with our new probability maps was more anatomically plausible compared to the one derived with currently available priors. We provide evidence that the improved delineation compensates age-related bias in the segmentation of iron rich subcortical regions. The new tissue priors, allowing robust detection of basal ganglia and thalamus, have the potential to enhance the sensitivity of voxel-based morphometry in both healthy and diseased brains.

ICG Fluorescence Technique for the Detection of Sentinel Lymph Nodes in Breast Cancer: Results of a Prospective Open-label Clinical Trial.

Introduction: Detection of sentinel lymph nodes (SLN) is the standard procedure to evaluate axillary lymph node status in breast cancer. In addition to known and established procedures such as the blue dye method and scintigraphy, this study investigated the efficacy of a method based on use of the fluorescent dye indocyanine green (ICG). Patients and Method: A total of 126 women with breast cancer histologically verified by punch biopsy were studied during surgical removal of SLN. In addition to SLN marking with technetium and scintigraphy, intra-individual comparison was done using indocyanine green (ICG) for marking instead of the standard blue dye. Results: Scintigraphy had a detection rate of 96 %; the detection rate with ICG was just under 89 %. A body mass index (BMI) > 40 was found to be a limiting factor for the fluorescent method. Investigation into potential toxicities associated with the use of the fluorescent dye ICG revealed no systemic or even local side effects. The fluorescent method was found to be significantly less expensive than the scintigraphy method. Conclusion: The ICG fluorescence technique for the detection of SLN was found to be a valid and feasible method in clinical practice when compared directly with the blue dye method and scintigraphy.

Disentangling in vivo the effects of iron content and atrophy on the ageing human brain.

Evidence from magnetic resonance imaging (MRI) studies shows that healthy aging is associated with profound changes in cortical and subcortical brain structures. The reliable delineation of cortex and basal ganglia using automated computational anatomy methods based on T1-weighted images remains challenging, which results in controversies in the literature. In this study we use quantitative MRI (qMRI) to gain an insight into the microstructural mechanisms underlying tissue ageing and look for potential interactions between ageing and brain tissue properties to assess their impact on automated tissue classification. To this end we acquired maps of longitudinal relaxation rate R1, effective transverse relaxation rate R2* and magnetization transfer - MT, from healthy subjects (n=96, aged 21-88 years) using a well-established multi-parameter mapping qMRI protocol. Within the framework of voxel-based quantification we find higher grey matter volume in basal ganglia, cerebellar dentate and prefrontal cortex when tissue classification is based on MT maps compared with T1 maps. These discrepancies between grey matter volume estimates can be attributed to R2* - a surrogate marker of iron concentration, and further modulation by an interaction between R2* and age, both in cortical and subcortical areas. We interpret our findings as direct evidence for the impact of ageing-related brain tissue property changes on automated tissue classification of brain structures using SPM12. Computational anatomy studies of ageing and neurodegeneration should acknowledge these effects, particularly when inferring about underlying pathophysiology from regional cortex and basal ganglia volume changes.

A Novel SLC6A8 Mutation in a Large Family with X-Linked Intellectual Disability: Clinical and Proton Magnetic Resonance Spectroscopy Data of Both Hemizygous Males and Heterozygous Females.

X-linked creatine transport (CRTR) deficiency, caused by mutations in the SLC6A8 gene, leads to intellectual disability, speech delay, epilepsy, and autistic behavior in hemizygous males. Additional diagnostic features are depleted brain creatine levels and increased creatine/creatinine ratio (cr/crn) in urine. In heterozygous females the phenotype is highly variable and diagnostic hallmarks might be inconclusive. This survey aims to explore the intrafamilial variability of clinical and brain proton Magnetic Resonance Spectroscopy (MRS) findings in males and females with CRTR deficiency. X-chromosome exome sequencing identified a novel missense mutation in the SLC6A8 gene (p.G351R) in a large family with X-linked intellectual disability. Detailed clinical investigations including neuropsychological assessment, measurement of in vivo brain creatine concentrations using quantitative MRS, and analyses of creatine metabolites in urine were performed in five clinically affected family members including three heterozygous females and one hemizygous male confirming the diagnosis of CRTR deficiency. The severe phenotype of the hemizygous male was accompanied by most distinct aberrations of brain creatine concentrations (-83% in gray and -79% in white matter of age-matched normal controls) and urinary creatine/creatinine ratio. In contrast, the heterozygous females showed varying albeit generally milder phenotypes with less severe brain creatine (-50% to -33% in gray and -45% to none in white matter) and biochemical urine abnormalities. An intrafamilial correlation between female phenotype, brain creatine depletion, and urinary creatine abnormalities was observed. The combination of powerful new technologies like exome-next-generation sequencing with thorough systematic evaluation of patients will further expand the clinical spectrum of neurometabolic diseases.

The HER2 status of disseminated tumor cells in the bone marrow of early breast cancer patients is independent from primary tumor and predicts higher risk of relapse.

Overexpression of the HER2-receptor in early breast cancer (EBC) patients is associated with aggressive tumor behavior. However, women suffering from HER2-positive EBC benefit from trastuzumab treatment. As the HER2 status of the primary tumor may differ from that of disseminated tumor cells (DTC) in bone marrow (BM), the aim of this study was (1) to compare the HER2 status of the primary tumor (prim-HER2-status) with that of DTC (DTC-HER2-status) and (2) to analyze the influence of the DTC-HER2-status on patient survival. For this purpose, BM aspirates from 569 EBC patients were analyzed for the presence of DTC. The DTC-HER2-status was identified by a double-staining procedure against cytokeratin and the HER2-receptor. DTC were detected in 151 (27 %) patients. The concordance between the HER2 status of DTC and the primary tumor was 51 %. In patients with detectable DTC, mean disease-free survival was 77.44 (95 % CI 74.72-80.17) months for DTC-HER2-negative and 55.15 (95 % CI 48.57-61.79) months for DTC-HER2-positive patients (p = 0.044). The multivariate analysis showed that the DTC-HER2-status was an independent predictor of disease-free survival. In conclusion, the presence of HER2-positive DTC in EBC patients is associated with an increased risk of relapse. Due to the low concordance between the HER2 status of the primary tumor and DTC, only a minority (13 %) of the DTC-HER2-positive patients was treated with trastuzumab. These patients might, however, benefit from HER2-directed therapy.

Increased growth of colorectal liver metastasis following partial hepatectomy.

Nearly 50 % of colorectal cancer (CRC) patients develop liver metastases with liver resection being the only option to cure patients. Residual micrometastases or circulating tumor cells are considered a cause of tumor relapse. This work investigates the influence of partial hepatectomy (PH) on the growth and molecular composition of CRC liver metastasis in a syngeneic rat model. One million CC531 colorectal tumor cells were implanted via the portal vein in WAG/Rij rats followed by a 30 % PH a day later. Control groups either received tumor cells followed by a sham-operation or were injected with a buffer solution followed by PH. Animals were examined with magnetic resonance imaging (MRI) and liver tissues were processed for immunolabeling and PCR analysis. One-third PH was associated with an almost threefold increase in relative tumor mass (MRI volumetry: 2.8-fold and transcript levels of CD44: 2.3-fold). Expression of molecular markers for invasiveness and aggressiveness (CD49f, CXCR4, Axin2 and c-met) was increased following PH, however with no significant differences when referring to the relative expression levels (relating to tumor mass). Liver metastases demonstrated a significantly higher proliferation rate (Ki67) 2 weeks following PH and cell divisions also increased in the surrounding liver tissue. Following PH, the stimulated growth of metastases clearly exceeded the compensation in liver volume with long-lasting proliferative effects. However, the distinct tumor composition was not influenced by liver regeneration. Future investigations should focus on the inhibition of cell cycle (i.e. systemic therapy strategies, irradiation) to hinder liver regeneration and therefore restrain tumor growth.

Assessment of myelination in hypomyelinating disorders by quantitative MRI.

PURPOSE: To apply myelin-sensitive quantitative magnetic resonance imaging (MRI) techniques in defined hypomyelinating conditions and to identify spatial patterns of myelination as criteria for characterization of undefined disorders. MATERIALS AND METHODS: Seven patients were included, based on the diagnosis of mitochondrial cytopathy, Pelizaeus-Merzbacher disease, GJA12/GJC2-related Pelizaeus-Merzbacher-like disease, hypomyelination with atrophy of the basal ganglia and cerebellum, and leukoencephalopathy with ataxia, delayed dentition, and hypomyelination. The control group comprised 23 children and adolescents (age range 2.6-22.4 years). The 3T MRI protocol consisted of high-resolution T1- and T2-weighted 3D MRI, diffusion tensor (DTI), and magnetization transfer (MT) imaging. Parameter maps of mean diffusivity, fractional anisotropy, and MT saturation were displayed as pseudocolor overlays and assessed by region-of-interest and histogram analysis. RESULTS: Structural MRI revealed widespread signal alterations in white matter, but were hampered by signal heterogeneity. Quantitative DTI and MT reflected the degree of hypomyelination and discriminative patterns of myelination emerged on MT saturation maps. CONCLUSION: The quantitative parameters in the defined hypomyelination conditions provide additional criteria to further classify undefined white matter disorders.

Differentiation of typical and atypical Parkinson syndromes by quantitative MR imaging.

BACKGROUND AND PURPOSE: The differential diagnosis of Parkinson syndromes remains a major challenge. Quantitative MR imaging can aid in this classification, but it is unclear which of the proposed techniques is best suited for this task. We, therefore, conducted a head-to-head study with different quantitative MR imaging measurements in patients with IPS, MSA-type Parkinson, PSP, and healthy elderly controls. MATERIALS AND METHODS: Thirty-one patients and 13 controls underwent a comprehensive quantitative MR imaging protocol including R2*-, R2- and R1-mapping, magnetization transfer, and DTI with manual region-of-interest measurements in basal ganglia regions. Group differences were assessed with a post hoc ANOVA with a Bonferroni error correction and an ROC. RESULTS: The best separation of MSA from IPS in patients and controls could be achieved with R2*-mapping in the PU, with an ROC AUC of ≤0.96, resulting in a sensitivity of 77.8% (with a specificity 100%). MD was increased in patients with PSP compared with controls and to a lesser extent compared with those with IPS and MSA in the SN. CONCLUSIONS: Among the applied quantitative MR imaging methods, R2*-mapping seems to have the best predictive power to separate patients with MSA from those with IPS, and DTI for identifying PSP.

Multi-site voxel-based morphometry--not quite there yet.

Voxel-based morphometry (VBM) is a widely applied method in computational neurosciences but it is currently recommended to compare only data collected at a single MRI scanner. Multi-site VBM would be a desirable approach to increase group size and, thus, statistical power. We aimed to assess if multi-site VBM is feasible on similar hardware and compare the magnitude of inter- and intra-scanner differences. 18 healthy subjects were scanned in two identical 3T MRI scanners using different head coil designs, twice in scanner A and once in scanner B. 3D T1-weighted images were processed with SPM8 and FSL4.1 and compared as paired t-test (scan versus re-scan) on a voxel basis by means of a general linear model (GLM). Additionally, coefficient-of-difference (coeffD) maps were calculated for respective pairs of gray matter segmentations. We found considerable inter-scanner differences clearly exceeding a commonly used GLM significance threshold of p<0.05 (FWE corrected). The spatial pattern of detected differences was dependent on whether SPM8 or FSL4.1 was used. The inclusion of global correcting factors either aggravated (SPM8) or reduced the GLM detected differences (FSL4.1). The coeffD analysis revealed markedly higher variability within the FSL4.1 stream both for the inter- and the intra-scanner comparison. A lowered bias cutoff (30 mm FWHM) in SPM8 improved the comparability for cortical areas. Intra-scanner scan/re-scan differences were generally weaker and did not exceed a p<0.05 (FWE corrected) threshold in the GLM analysis. At 3T profound inter-scanner differences are to be expected that could severely confound an unbalanced VBM analysis. These are like related to the receive bias of the radio-frequency hardware.

Regional specificity of MRI contrast parameter changes in normal ageing revealed by voxel-based quantification (VBQ).

Normal ageing is associated with characteristic changes in brain microstructure. Although in vivo neuroimaging captures spatial and temporal patterns of age-related changes of anatomy at the macroscopic scale, our knowledge of the underlying (patho)physiological processes at cellular and molecular levels is still limited. The aim of this study is to explore brain tissue properties in normal ageing using quantitative magnetic resonance imaging (MRI) alongside conventional morphological assessment. Using a whole-brain approach in a cohort of 26 adults, aged 18-85years, we performed voxel-based morphometric (VBM) analysis and voxel-based quantification (VBQ) of diffusion tensor, magnetization transfer (MT), R1, and R2* relaxation parameters. We found age-related reductions in cortical and subcortical grey matter volume paralleled by changes in fractional anisotropy (FA), mean diffusivity (MD), MT and R2*. The latter were regionally specific depending on their differential sensitivity to microscopic tissue properties. VBQ of white matter revealed distinct anatomical patterns of age-related change in microstructure. Widespread and profound reduction in MT contrasted with local FA decreases paralleled by MD increases. R1 reductions and R2* increases were observed to a smaller extent in overlapping occipito-parietal white matter regions. We interpret our findings, based on current biophysical models, as a fingerprint of age-dependent brain atrophy and underlying microstructural changes in myelin, iron deposits and water. The VBQ approach we present allows for systematic unbiased exploration of the interaction between imaging parameters and extends current methods for detection of neurodegenerative processes in the brain. The demonstrated parameter-specific distribution patterns offer insights into age-related brain structure changes in vivo and provide essential baseline data for studying disease against a background of healthy ageing.

In vivo proton MR spectroscopy findings specific for adenylosuccinate lyase deficiency.

Adenylosuccinate lyase (ADSL) deficiency is an inherited metabolic disorder affecting predominantly the central nervous system. The disease is characterized by the accumulation of succinylaminoimidazolecarboxamide riboside and succinyladenosine (S-Ado) in tissue and body fluids. Three children presented with muscular hypotonia, psychomotor delay, behavioral abnormalities, and white matter changes on brain MRI. Two of them were affected by seizures. Screening for inborn errors of metabolism including in vitro high resolution proton MRS revealed an ADSL deficiency that was confirmed genetically in all cases. All patients were studied by in vivo proton MRS. In vitro high resolution proton MRS of patient cerebrospinal fluid showed singlet resonances at 8.27 and 8.29 ppm that correspond to accumulated S-Ado. In vivo proton MRS measurements also revealed a prominent signal at 8.3 ppm in gray and white matter brain regions of all patients. The resonance was undetectable in healthy human brain. In vivo proton MRS provides a conclusive finding in ADSL deficiency and represents a reliable noninvasive diagnostic tool for this neurometabolic disorder.

Shoulder-arm morbidity in patients with sentinel node biopsy and complete axillary dissection--data from a prospective randomised trial.

BACKGROUND: Axillary lymph node dissection (ALND) as part of surgical treatment in breast cancer has been the standard procedure for many decades. However, patients frequently develop shoulder-arm morbidity postoperatively. Recently, sentinel node (SN) biopsy has been established as a new standard of care for axillary staging in breast cancer. This study compares postoperative morbidity between ALND and SN biopsy. The results are compared with the existing literature. METHOD: Between November 2000 and September 2002, 181 women with early stage breast cancer underwent primary surgery following preoperative randomisation into two groups, a "standard group" (SN biopsy was followed by ALND) and a study group (surgical procedure consisting of only SN biopsy when histologically metastasis-free SN was present). Follow-up data (362 sessions; 6 months to 3 years after primary surgery) were available from 150 patients. A summary morbidity score was calculated from four subjective (arm-strength, arm-mobility, arm swelling, pain) and four objective (arm-strength, arm-mobility, lymphedema, sensitivity) criteria. RESULTS: Fifty seven patients underwent SN biopsy only. Ninety three patients underwent ALND, 57 of which had lymph nodes free of metastasis and 36 had lymph nodes with metastasis and axillary clearing. Shoulder-arm morbidity was significantly different between the groups. Patients treated with SN biopsy only scored better on subjective and objective criteria. SUMMARY: Postsurgical shoulder-arm morbidity is a major long-term problem in patients undergoing surgical treatment for breast cancer. This prospective study showed significantly less severe shoulder-arm morbidity following SN biopsy compared to patients undergoing ALND.

Improved visibility of the subthalamic nucleus on high-resolution stereotactic MR imaging by added susceptibility (T2*) contrast using multiple gradient echoes.

Reliable identification of the subthalamic nucleus (STN) is a critical step in deep brain stimulation for Parkinson disease but difficult on T1-weighted stereotactic MR imaging. By simultaneous imaging of multiple gradient echoes, susceptibility contrast is added to conventional T1-weighted high-resolution MR image. Thus, the visibility of the STN is enhanced on a second co-localized dataset by exploiting the sensitivity of the T2*-relaxation to local iron deposits. The feasibility is underpinned by quantitative measurements on healthy adults.

Increased thalamus levels of glutamate and glutamine (Glx) in patients with idiopathic generalised epilepsy.

OBJECTIVE: Abnormal thalamo-cortical oscillations underlie idiopathic generalised epilepsy (IGE). Although thalamic involvement has long been indicated by electrophysiological data, it has only recently become feasible to test this with independent methods. In this magnetic resonance (MR) study, we investigated the metabolic and structural integrity of the thalamus. Possible changes in glutamine and glutamate concentrations and signs of neuronal damage were of particular interest. METHOD: Forty three IGE patients and 38 age and sex matched healthy controls were investigated. Quantitative single volume MR spectroscopy (MRS, 1.5 T) was used to measure concentrations of glutamate and glutamine (Glx) and N-acetyl aspartate (NAA) in thalamus and occipital cortex. We also measured thalamic volumes on high resolution gradient-echo images and estimated fractions of thalamic grey and white matter with voxel based morphometry (VBM). RESULTS: IGE patients showed elevated Glx and reduced NAA concentrations in the thalamus compared to controls (12.2+/-2.6 v 8.9+/-4.1 mM, p = 0.0022 for Glx, and 9.9+/-1.0 v 10.7+/-0.9 mM, p = 0.017 for NAA). Thalamic grey matter fraction was reduced in IGE patients, and white matter fraction was increased with the greatest increase in the dorso-medial thalamus. Mean thalamic volume was reduced in patients (6.7+/-0.7 v 7.2+/-0.6 ml in controls, p = 0.0001), as was mean cerebral volume (1163+/-128 v 1250+/-102 ml, p = 0.0003). Patients' thalamus/whole brain ratios were normal. CONCLUSION: Quantitative MRS and VBM provide further evidence for involvement of the thalamus in IGE. The observed elevation of Glx levels together with reductions in NAA levels and grey matter fractions are consistent with epilepsy related excitoxicity as a possible underlying mechanism.

[Determination of the elastic properties of the compact bone in the femur of dogs]. / Ermittlung der elastischen Eigenschaften der Kompakta im Femur des Hundes.

Total hip endoprotheses are a good possibility for treatment degenerative wear and pathologic damage of the hip joint in man as well as in dogs. However, aseptic loosening of the protheses, especially in the area of the shaft, is still a problem in conventional total hip endoprotheses. The purpose of the present study was to use the finite-element-analysis (FEA), to enhance endoprothetic design and to prevent loosening of protheses. In order to simulate the femur of the dog for numerical analysis, a material law for the compacta in the femur of the dog was developed. The elastic properties of the compacta were experimentally determined by using compression tests of bone samples of euthanised dogs. The results show constant denseness and a constant axial elastic modul in the compacta.