T Nägele

Universitätsklinikum Tübingen, Tübingen, Baden-Württemberg, Germany

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Publications (234)664.66 Total impact

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    ABSTRACT: Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is caused by autosomal-dominantly inherited mutations in the colony stimulating factor 1 receptor (CSF1R) gene, and is clinically characterized by a progressive cognitive and motor decline leading to death within several years. In a continuous series of 25 patients with adult-onset leukoencephalopathy of unknown cause, we genetically confirmed HDLS in 6 families. Affected and nonaffected individuals were examined clinically and by brain MRI studies. HDLS presented as prominent dementia and apraxia, often with extrapyramidal and pyramidal signs, rarely with ataxia. White matter MRI changes were detectable early in the disease course. Family history was negative in 4 of 6 index patients. In 2 of 6 index patients, we could confirm the occurrence of de novo mutations in the CSF1R gene. One family showed possible incomplete penetrance: the 69-year-old father of the index patient carried a CSF1R mutation but was clinically unaffected. In one family, the parents were apparently unaffected and not available for genetic testing. Typical clinical phenotype and early brain MRI alterations can help to guide the diagnosis of HDLS. Because we confirmed de novo mutations in one-third of patients with CSF1R mutations, this diagnosis should be considered even in the absence of a family history. Furthermore, we present evidence for reduced penetrance of a CSF1R mutation. These results have substantial impact for genetic counseling of asymptomatic individuals at risk and should foster research into disease-modifying factors.
    Neurology 11/2013; · 8.25 Impact Factor
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    ABSTRACT: The means of identifying prostate carcinoma and its metastases are limited. The contrast agents used in magnetic resonance imaging clinical diagnostics are not taken up into the tumor cells, but only accumulate in the interstitial space of the highly vasculated tumor. We examined the gastrin/cholecystokinin-B receptor as a possible target for prostate-specific detection using the C-terminal seven amino acid sequence of the gastrin peptide hormone. The correct sequence and a scrambled control sequence were coupled to the fluorescent dye rhodamine and the magnetic resonance imaging contrast agent gadolinium (Gd)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Expression analysis of the gastrin receptor mRNA was performed by reverse transcriptase polymerase chain reaction on PC3 prostate carcinoma cells, U373 glioma, U2OS osteosarcoma and Colo205 colon carcinoma cells. After having confirmed elevated expression of gastrin receptor in PC3 cells and very low expression of the receptor in Colo205 cells, these two cell lines were used to create tumor xenografts on nude mice for in vivo experiments. Confocal lasers scanning microscopy and magnetic resonance imaging showed a high specificity of the correct conjugate for the PC3 xenografts. Staining of the PC3 xenografts was much weaker with the scrambled conjugate while the Colo205 xenografts showed no marked staining with any of the conjugates. In vitro experiments comparing the correct and scrambled conjugates on PC3 cells by magnetic resonance relaxometry and fluorescence-activated cell sorting confirmed markedly higher specificity of the correct conjugate. The investigations show that the gastrin receptor is a promising tumor cell surface target for future prostate-cancer-specific imaging applications.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 11/2013; · 2.61 Impact Factor
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    ABSTRACT: Diffusion magnetic resonance imaging (MRI) is commonly used in acute stroke, but not considered diagnostic in ischemic optic neuropathy. This study evaluates the presence of diffusion restriction in patients with acute visual loss by analyzing diffusion-weighted images (DWI). A retrospective study of all patients who clinically presented with acute visual loss and who underwent MRI with DWI between January 2011 and May 2012 were evaluated. Patients with suspected brainstem ischemia were used as a control group. Two neuroradiologists evaluated the DWI for the presence of diffusion restriction within the optic nerve. In all, 34 patients with acute visual deficit and 32 controls were evaluated. In all five cases of acute optic ischemia, diffusion restriction with reduced apparent diffusion coefficient was present. In 2/25 patients with clinically defined optic neuritis, a diffusion restriction was present. No diffusion restriction was seen in the control cases or in cases with other causes for an acute visual deficit. DWI can identify ischemic lesions of the optic nerve. As in acute multiple sclerosis lesions, optic neuritis can also present in rare circumstances with diffusion restriction and can therefore not be ruled out solely by DWI MRI. J. Magn. Reson. Imaging 2013. © 2013 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 11/2013; · 2.57 Impact Factor
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    ABSTRACT: MR spectroscopy (MRS) measurements are common practice in the preoperative diagnostic regimen, but no evidence exists concerning their value in intraoperative MRI (iMRI) setting. We sought to examine the feasibility of intraoperative MRS and to assess the clinical value of the method in optimizing the gliomas resection. Forty-five patients with low- and high-grade gliomas underwent iMRI-assisted surgery, including pre- and intraoperative MRS measurements. During the intraoperative control scan, MRS was performed at the resection margin. Peak areas under the major metabolites (N-acetyl-aspartate: NAA; choline: Cho; and creatine: Cr) resonances were estimated, and their ratios entered in the statistical analysis. Concerning preoperative MRS imaging, mean Cho/NAA and Cho/Cr ratios in low-grade gliomas were 2.3 and 1.2, respectively. The average Cho/NAA and Cho/Cr ratios in the high-grade gliomas were 3.9 and 2.3, respectively. In 12 out of 20 cases with low-grade gliomas, intraoperative conventional MR imaging showed suspected tumor remnant and MRS diagnosed correctly the tissue signal alterations in 10 out of those 12 cases. MRS could characterize gadolinium-enhancing or non-enhancing tumor remnants in all cases with high-grade tumors. Thus, it could help achieve total tumor resection unless the latter was contraindicated due to increased risk of neurological complications. MR spectroscopy (MRS) in an iMRI setting is feasible, facilitating preoperative glioma staging as well as satisfactory characterization of suspected tumor remnants. Thus, it may be helpful tool for an extended tumor resection.
    International Journal of Computer Assisted Radiology and Surgery 10/2013; · 1.36 Impact Factor
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    W. Grodd, M. Skalej, T. Nägele, K. Voigt
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    ABSTRACT: The antitumor activity of antibacterial and antifungal compounds has been of interest in the past. In several investigations glycopeptide antibiotics like bleomycin and antifungal agents like itraconazole have shown direct positive results whereas antifungal polyenes such as amphotericin B have been shown to potentiate the effects of antitumor agents. After having investigated the fluorescence-marked antibacterial glycopeptides vancomycin and ramoplanin on various malignant and healthy human cells in previous studies, the present work is focused on the antifungal polyene nystatin. We coupled nystatin to the fluorescent dye fluorescein isothiocyanate (FITC). After confirming the correct mass by mass spectrometry the effect of the conjugate on nine different human cell lines (two benign and seven tumor cell lines) was examined. The character of the uptake was determined by confocal laser scanning microscopy (CLSM) and the uptake was quantified by fluorescence activated cell sorting (FACS). The addition of propidium iodide (PI) allowed for detection and quantification of cell membrane disruption caused by the fluorescein-nystatin conjugate. Uptake of the conjugate was found to vary among the nine cell lines investigated. Conjugate uptake was strongest after 6 hours in most cell lines. Only the two prostate carcinoma cell lines PC3 and LNCaP showed further increase in uptake after long-time (24h) incubation. PI staining in general correlated well with the conjugate FITC staining values. The Colo205 colon carcinoma cell line and the U373 and LN18 glioblastoma cell lines exhibited very low conjugate uptake and PI staining. The results indicate that this conjugate shows potential for future imaging studies on certain human cancer cells.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 06/2013; · 1.64 Impact Factor
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    ABSTRACT: The gastrin releasing peptide receptor (GRPR) has been found to be strongly expressed in various types of cancers such as prostate and breast carcinomas. The GRPR ligands gastrin releasing peptide and bombesin can play a very significant role in cancer therapy and diagnostics. In this study we synthesized unlabeled bombesin BBN along with two conjugates in which the correct bombesin (BBN-Rhd) and a mutant bombesin (mBBN-Rhd) sequence was coupled to rhodamine, a fluorescent dye. These novel rhodamine fluorescent conjugates were used to study the targeting and uptake of bombesin on a cellular level. Nine different human cell lines including both tumor and healthy cells were examined using flow cytometry and confocal laser scanning microscopy. GRPR mRNA expression analysis was performed and it was found that the receptor is highly expressed in LNCaP and PC3 cells compared to the rest of other cell lines. Competition experiments were performed to verify the receptor dependence of the labeled conjugates using unmarked bombesin. The present study is a first attempt at direct fluorescence imaging of living cells using bombesin and its target, the GRPR. A rhodamine bombesin conjugate can be used as marker to differentiate between healthy cells and malignant cells such as prostate hyperplasia and prostate carcinoma in the early detection of cancer.
    Investigational New Drugs 06/2013; · 3.50 Impact Factor
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    ABSTRACT: In a previous study we found that fluorescence-marked vancomycin - a glycopeptide antibiotic - is taken up into human tumor cells. To expand on these investigations we now used the lipoglycodepsipeptide antibiotic ramoplanin. Compared to vancomycin it is a bigger molecule but it also has two potential binding sites for coupling to the imaging agents. Three different ramoplanin imaging conjugates were synthesized, two used for fluorescence imaging and one for magnetic resonance imaging. The two fluorescent dyes used in confocal laser scanning microscopy (CLSM) and fluorescence activated cell sorting (FACS) were fluorescein isothiocyanate (FITC) and rhodamine isothiocyanate (RITC). The third was the magnetic resonance imaging (MRI) contrast agent gadolinium-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (GdDOTA). The uptake of ramoplanin conjugates, their specificity for different cell lines and the accessibility of the conjugates by imaging methods was evaluated on 8 human cell lines (two benign, six malignant) by CLSM, FACS and MRI experiments. Cytotoxicity of the ramoplanin conjugates was determined in the FACS experiments with the propidium iodide and Annexin-V-Fluos indicating any disruption in the cell membranes. Cytoplasmic uptake of the ramoplanin conjugates was observed in confocal laser scanning images and was measured using FACS and MRI experiments. Compared to the vancomycin conjugates the ramoplanin conjugates showed much weaker and slower uptake. Additionally, uptake of the ramoplanin conjugates led to strong membrane disruption and cell death.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 05/2013; · 1.64 Impact Factor
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    ABSTRACT: The methods used for detection of prostate cancer and prostate cancer lymph node metastases in medical diagnostics leave room for improvement. Currently, no means of identifying metastasized lymph nodes other than biopsies is available. Markers which are exclusively found on prostate cancer cells present a focal point for potential imaging methods. To complement the established markers like e.g. PCA3-a noncoding mRNA sequence-and PSA-a serine protease-we investigated the ectopically expressed G-protein coupled olfactory receptor OR1D2 as a possible target for prostate-specific detection with its agonist bourgeonal which has been conjugated to two different fluorescent dyes. We performed mRNA expression analysis of the OR1D2 receptor mRNA by reverse transcriptase polymerase chain reaction on LNCaP prostate carcinoma cells and three other non-prostate derived carcinoma cell lines. Additionally, we used flow cytometry to investigate the uptake of fluorescent-dye-bound OR1D2-ligand bourgeonal into the examined carcinoma cell lines. Finally, confocal laser scanning microscopy of in vitro cell culture and in vivo tumor xenografts on mice was performed. We could confirm OR1D2 receptor mRNA overexpression as well as stronger uptake of both bourgeonal conjugates in vitro and in vivo for LNCaP cells compared to the non-prostate derived cell lines. Cytoplasmic accumulation and no adverse effects after in vitro and in vivo application of the conjugates were observed. The conjugates represent a platform for the development of future prostate-specific imaging applications, e.g. detection of metastasized lymph nodes during surgery by intraoperative laser examination.
    Investigational New Drugs 03/2013; · 3.50 Impact Factor
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    ABSTRACT: Cerebral infections may develop into a life-threatening condition. Fast and correct diagnosis is crucial for a differentiated therapy and MRI imaging is widely accepted as the method of choice. Both specific MR sequences and imaging characteristics of major cerebral infections are addressed in this overview. Furthermore, limitations and pitfalls of the method are discussed.
    RöFo - Fortschritte auf dem Gebiet der R 03/2013; · 2.76 Impact Factor
  • RöFo - Fortschritte auf dem Gebiet der R 03/2013; 185(3):195-8. · 2.76 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: The most powerful adjunct to histopathology for the grading of gliomas seems to be the metabolic imaging using positron emission tomography and magnetic resonance spectroscopy (MRS). The purposes of this study were to examine the feasibility of simultaneous acquisition of both techniques for purposes of tumor grading in a newly launched hybrid magnetic resonance positron emission tomography (MR-PET) and to examine the spatial distributions of metabolic changes in gliomas. MATERIALS AND METHODS: Twenty-eight consecutive patients with gliomas underwent simultaneous methionine (Met) MR-PET imaging for detection of the most malignant tumor part before surgical sampling. After coregistration and fusion of MR-PET and MRS data, tumor to normal brain (T/N) Met uptake ratios and the corresponding metabolites peaks (choline [Cho], creatine [Cr], and N-acetylaspartate [NAA]) in MRS were recorded. The patients were divided into 4 types on the basis of the relation between the Met uptake area and the increased metabolite ratios: type I, the increased Met uptake area had at least 50% overlap or was completely within the area of increased Cho/NAA ratio; type II, the increased Met uptake site had less than 50% overlap of increased Cho/NAA ratio site; type III, the increased Met uptake region had no spatial relationship with the "hot" lesions in the MRS maps; and type IV, there was no pathologically increased Met uptake. The surgical sampling was performed in the tumor part with the highest Met uptake and, in the absence of increased Met accumulation, in the site with the highest Cho/NAA ratio. All surgical samples were referred to the neuropathology division for histological grading. RESULTS: A total of 16 low-grade gliomas (World Health Organization grade II) and 12 high-grade gliomas (World Health Organization grade III) were included. Three lesions (10%) of type I were identified. Four lesions (14%) were classified as type II and 6 lesions (21%) were classified as type 3, where the increased Met uptake region had no spatial relationship with the hot lesions in the MRS maps. In 15 of the 28 patients (54%), there was no increased Met accumulation (type 4 lesions). Maps of Cho/NAA and Cr/NAA showed a close spatial relationship in most of the patients. Median T/N Met uptake ratio in the pooled surgically sampled tumor sites was 1.6 (range, 1-3), and median Cho/NAA and Cho/Cr ratios were 2.1 (range, 0.9-5.8) and 1.5 (range, 0.5-8.3), respectively. Spearman rank correlations of the metabolic markers in the low-grade gliomas showed significant correlations between Met uptake and Cr/NAA ratio (ρ = 0.59; P= 0.015) as well as between Cho/NAA and Cr/NAA ratios (ρ = 0.79; P = 0.0002). The normalized tumor creatine was significantly higher in anaplastic tumors compared with the low-grade gliomas (P = 0.001). A tendency for a significant positive correlation was found between normalized tumor creatine and Met uptake in the anaplastic tumors. CONCLUSIONS: Metabolic mapping before histological sampling is feasible using simultaneous MR-PET imaging. High T/N Met uptake ratio reflecting high expression of amino-acid membrane transporters, which is indicative of proliferating tumor cell populations, does not always spatially correlate with neuronal cell loss and cell membrane proliferation (Cho/NAA) seen in MRS. Increased Cr/NAA is associated with increased methionine uptake in low-grade gliomas, whereas normalized creatine in tumor tends to correlate with methionine accumulation, which indicates a possible coupling of these metabolic indices in anaplastic tumors. Thus, spatial distribution differences in gliomas should be taken into account when planning surgical sampling.
    Investigative radiology 01/2013; · 4.85 Impact Factor
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    Uwe Klose, Marion Batra, Thomas Nägele
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    ABSTRACT: The aim of this study was to develop a fast method for estimating whether a brain volume loss is within the normal range for the respective age of the patient. A readout-segmented diffusion-weighted echo-planar imaging sequence was performed as part of the routine examination at a 3-T scanner. Data without (b0-image) and with diffusion weighting (1000 s/mm(2)) from 492 patients were examined (in the age from 3 to 89 years). One hundred and seventy-three data-sets had to be excluded due to brain lesions or to pathological enlarged cerebrospinal fluid spaces. In the remaining 319 data-sets, apparent diffusion coefficients (ADCs) values were calculated for all pixels exceeding a combined threshold in the diffusion-weighted data and in the non-diffusion-weighted data. The first part of the histogram represents pixels containing mostly brain tissue. The percentage of number of pixels in this part of the ADC histograms was evaluated for all patients and was correlated with the age of the patients. In all the areas examined, a monotone change of relative pixel numbers with the age of the patients was found. The reduction of the contribution of pixels containing mostly brain tissue accelerated with age and was found to be 0.18%/year in the age of 20, 0.34%/year in the age of 50, and 0.50%/year in the age of 80. The observed decrease of the relative number of pixels from the brain tissue with increasing age corresponds to previously published results based on more time-consuming 3-D measurements. The presented technique uses a conventional clinical sequence and might be helpful in deciding whether an observed brain volume loss in a patient is within the normal range for the age of the patient.
    Frontiers in Aging Neuroscience 01/2013; 5:78. · 5.20 Impact Factor
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    ABSTRACT: Aims A safe total resection followed by adjuvant chemoradiotherapy should be the primary goal in the treatment of glioblastomas (GBMs) to enable patients the longest survival possible. 5-aminolevulinic acid (5-ALA)- and intraoperative MRI (iMRI)-assisted surgery, have been shown in prospective randomized trials to significantly improve the extent of resection (EOR) and subsequently survival of patients with GBMs. No direct comparison of surgical results between both techniques has been published to date. We analyzed the additional value of iMRI in glioblastoma surgery compared to conventional surgery with and without 5-ALA. Methods Residual tumor volumes, clinical parameters and 6-month progression-free survival (6M-PFS) rates after GBM resection were analyzed retrospectively for 117 patients after conventional, 5-ALA and iMRI-assisted surgery. Results Mean residual tumor volume (range) after iMRI-assisted surgery [0.5 (0.0–4.7) cm3] was significantly smaller compared to the residual tumor volume after 5-ALA-guided surgery [1.9 (0.0–13.2) cm3; p = .022], which again was significantly smaller than in conventional white-light surgery [4.7 (0.0–30.6) cm3; p = .007]. Total resections were significantly more common in iMRI- (74%) than in 5-ALA-assisted (46%, p = .05) or white-light surgery (13%, p = .03). Improvement of the EOR by using iMRI was safely achievable as peri- and postoperative morbidities were comparable between cohorts. Total resections increased 6M-PFS from 32% to 45%. Conclusions Analysis of residual tumor volumes, total resections and neurological outcomes demonstrate that iMRI may be significantly superior to 5-ALA and white-light surgery for glioblastomas at comparable peri- and postoperative morbidities. Longer 6M-PFS was observed in patients with total resections.
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 01/2013; · 2.56 Impact Factor
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    ABSTRACT: BACKGROUND:: High-field, intraoperative MR imaging (iMRI) achieves free tumor margins in glioma surgery by involving anatomical neuronavigation and sophisticated functional imaging. OBJECTIVE:: To evaluate the role of perfusion-weighted iMRI as an aid to detect residual tumor and guide its resection. METHODS:: Twenty-two patients undergoing intraoperative scanning (in a dual-room 1.5-T magnet setting) during the resection of high-grade gliomas were examined with perfusion-weighted iMRI. The generated relative cerebral blood volume (rCBV) maps were scrutinized for any hot spots, indicative of tumor remnants, and region-of-interest (ROI) analysis was performed. Differences between the rCBV ROI-estimates in residual tumor, free tumor margins and normal white matter were analyzed. Histopathology of the tissue specimens and intraoperative neurosurgeon's macroscopical estimations were considered as reference standard. RESULTS:: In all cases, diagnostic rCBV perfusion maps were generated. The interpretation of perfusion maps demonstrated that gross total resection of gliomas was achieved in 4 (18%) of 22 cases, which was macroscopically and histopathologically verified, whereas in 18 (82%) of 22 cases, the perfusion-weighted iMRI revealed hot spots indicating subtotal tumor removal. The latter proved to be true in all but one case. The ROC curves of the qualitative visual and the quantitative analysis showed excellent sensitivity and specificity rates. The statistical analysis demonstrated statistically significant differences for the mean rCBV and maximum rCBV between residual disease and tumor free margins, (P = .0017) and (P = .0021) respectively. CONCLUSION:: Perfusion-weighted iMRI may be easily implemented into imaging protocols and may assist the surgeon in detecting residual tumor volume.
    Neurosurgery 11/2012; · 2.53 Impact Factor
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    ABSTRACT: Metachromatic leukodystrophy (MLD) is a rare inborn error of metabolism leading to severe neurological symptoms and early death. Hematopoietic SCT (HSCT) is considered a treatment option, but results are inconsistent and comparison with natural history is practically missing. We compare a girl with juvenile MLD 10 years after allogeneic HSCT not only with her untreated sister, but also with a large cohort of untreated patients. The girl received HSCT at the age of 5 years when first motor signs appeared. Over 10 years she was stable with respect to her clinical course and gained cognitive abilities. Magnetic resonance imaging (MRI) showed clear regression of white matter changes and magnetic resonance spectroscopy (MRS) demonstrated a reversal of the initial choline increase and N-acetyl-aspartate (NAA) decrease. Only axonal demyelinating neuropathy showed some progression. Her gross motor function and MRI-scores were clearly better compared with her sister and the cohort of untreated patients. Difference to her sister became apparent only 4 years after HSCT. We conclude that HSCT, early in the course of disease, can lead to stabilization of juvenile MLD with a course clearly different from the natural history. HSCT may prevent disease progression, if performed sufficient time before loss of walking, which typically initiates rapid deterioration.Bone Marrow Transplantation advance online publication, 3 September 2012; doi:10.1038/bmt.2012.155.
    Bone marrow transplantation 09/2012; · 3.00 Impact Factor
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    ABSTRACT: OBJECTIVE: The purpose of this article is to provide a practical review of the spectrum of imaging findings in patients with tick-borne encephalitis (TBE) and to address possible differential diagnoses. CONCLUSION: Imaging findings in TBE resemble those of other infections, such as meningoencephalitis. However, a predilection for the thalami, basal ganglia, cerebellum, and anterior horns of the spinal cord suggests the possibility of TBE.
    American Journal of Roentgenology 08/2012; 199(2):420-7. · 2.90 Impact Factor
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    ABSTRACT: OBJECTIVE: To provide a practical review of the spectrum of possible imaging findings in patients with progressive multifocal leukoencephalopathy (PML) and to address differentials. CONCLUSION: PML manifests with a broad spectrum of imaging features. Besides knowledge of preferential location, extent, temporal course, enhancement, results of functional imaging and clinical setting, recognition of imaging findings reflecting active demyelination may help the clinician in appropriately narrowing down the differential diagnosis.
    Clinical neurology and neurosurgery 07/2012; 114(8):1123-30. · 1.30 Impact Factor
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    ABSTRACT: To quantify and compare T2 signal and apparent diffusion coefficient (ADC) in pilocytic and pilomyxoid astrocytoma (PA and PMA) and correlate results with myxoid content. Echo-planar diffusion weighted images (DWI) and standard magnetic resonance imaging (MRI) findings were reviewed retrospectively in patients with PA (n=34) and PMA (n=8). Regions of interest (ROIs) were drawn on ADC maps within tumor parts with lowest ADC values. Apparent diffusion coefficient values in tumor were normalized to those in cerebrospinal fluid (ADC/CSF). The ratio of T2 signal intensity in solid tumor parts to CSF (T2/CSF) was registered. Myxoid matrix was histologically quantified retrospectively in 8 PMAs and 17 PAs and correlated with imaging findings. Mean ADC/CSF for PA and PMA was 0.53±0.10 and 0.69±0.10 (p<0.01). Mean T2/CSF for PA and PMA was 0.78±0.19 and 0.93±0.09 (p<0.01). Mean proportion of myxoid tumor matrix in PA was 50% (range, 10-100%) and 93% (range, 90-100%) in PMA (p=0.004). Eight patients (32%; all PA) had less than 50% myxoid content and 17 (68%; 8 PA; 9 PMA) had more. There was positive correlation of ADC/CSF, T2/CSF and ADC (r2=0.61, 0.65 and 0.60 respectively) and significant difference between the groups with more and less than 50% myxoid content (p=0.01 for ADC/CSF and T2/CSF and p=0.02 for ADC). General imaging features of PA and PMA are non-specific, ADC values and T2 signal intensity are generally higher in the latter, reflecting the proportion of myxoid matrix in these tumors.
    The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 07/2012; 39(4):491-8. · 1.33 Impact Factor
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    ABSTRACT: Our original aim was to evaluate in vivo nuclear uptake of a conjugate containing the SV40 T Antigen nuclear localization sequence (NLS), 6 aminohexanoic acids alternating with 7 arginines, the fluorescence dye fluorescein isothiocyanate (FITC) and the gadolinium chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). During the confocal laser scanning microscopy examination of frozen sections of the kidneys of mice injected intravenously with the conjugate we found unexpected conjugate relocation. In the dry frozen sections no nuclear staining was found. After covering the sections with physiological saline and a coverslip, the conjugate was relocated to the cell nuclei. Causation of this effect by FITC and DOTA could be excluded with appropriate controls. In the assumption that other positively charged conjugates behave in the same manner we tested two further conjugates in vivo. An octaarginine coupled to a lysine carrying FITC on the ε-amino-group was found in the cell nuclei of the frozen kidney sections before and after covering the slices with saline. By contrast, a conjugate containing myristoylated HIV-Tat was found not to stain the cell nuclei but only the cytoplasm before and after covering with saline. This demonstrates that not all positively charged conjugates are relocated to the cell nucleus after covering the frozen sections with saline. This was confirmed by direct incubation of frozen sections from untreated kidneys with the same conjugates and additional positively charged FITC conjugates. By coincubating the FITC conjugates with a cytoplasm directed rhodamine conjugate on untreated kidney sections we found that such conjugates could be used as nuclear FITC counterstain. In summary, one should bear in mind that positively charged conjugates applied in vivo can relocate artificially after covering with saline.
    Letters in Drug Design &amp Discovery 06/2012; 9:517-526. · 0.85 Impact Factor

Publication Stats

3k Citations
664.66 Total Impact Points

Institutions

  • 2004–2013
    • Universitätsklinikum Tübingen
      • • Division of Diagnostic and Interventional Neuroradiology
      • • Department of Neurosurgery
      • • Division of Neurourology
      Tübingen, Baden-Württemberg, Germany
  • 1993–2013
    • University of Tuebingen
      • • Hertie Institute for Clinical Brain Research
      • • Eye Hospital
      • • Department of Neurology
      • • Institute for Physiology
      Tübingen, Baden-Württemberg, Germany
  • 2005–2009
    • Hertie-Institute for Clinical Brain Research
      Tübingen, Baden-Württemberg, Germany
  • 2006
    • Universitätsmedizin Göttingen
      • Department of Neurology
      Göttingen, Lower Saxony, Germany
  • 1996
    • Országos Idegsebészeti Tudományos Intézet
      Budapeŝto, Budapest, Hungary