Radiomics and visual analysis for predicting success of transplantation of heterotopic glioblastoma in mice with MRI.

BACKGROUND: Quantifying tumor growth and treatment response noninvasively poses a challenge to all experimental tumor models. The aim of our study was, to assess the value of quantitative and visual examination and radiomic feature analysis of high-resolution MR images of heterotopic glioblastoma xenografts in mice to determine tumor cell proliferation (TCP). METHODS: Human glioblastoma cells were injected subcutaneously into both flanks of immunodeficient mice and followed up on a 3 T MR scanner. Volumes and signal intensities were calculated. Visual assessment of the internal tumor structure was based on a scoring system. Radiomic feature analysis was performed using MaZda software. The results were correlated with histopathology and immunochemistry. RESULTS: 21 tumors in 14 animals were analyzed. The volumes of xenografts with high TCP (H-TCP) increased, whereas those with low TCP (L-TCP) or no TCP (N-TCP) continued to decrease over time (p < 0.05). A low intensity rim (rim sign) on unenhanced T1-weighted images provided the highest diagnostic accuracy at visual analysis for assessing H-TCP (p < 0.05). Applying radiomic feature analysis, wavelet transform parameters were best for distinguishing between H-TCP and L-TCP / N-TCP (p < 0.05). CONCLUSION: Visual and radiomic feature analysis of the internal structure of heterotopically implanted glioblastomas provide reproducible and quantifiable results to predict the success of transplantation.

Effects of effective stereotactic radiosurgery for brain metastases on the adjacent brain parenchyma.

BACKGROUND: To evaluate whether functional and metabolic MRI can detect radiation-induced alterations in the adjacent areas after effective stereotactic radiosurgery (SRS) for brain metastases. If confirmed, these techniques may be suited for monitoring the timely stratification of patients for neuroprotective treatments after irradiation. METHODS: Inclusion criteria were complete response, partial response, or stable disease on routine follow-up MR-scans. Multiparametric 3T-MRI was performed with diffusion-weighted imaging, dynamic susceptibility perfusion-weighted imaging, and two-dimensional proton MR-spectroscopy. Parameters were measured in the SRS-treated target and in the adjacent parenchyma up to both 0.75 cm and 1.5 cm from the target border. RESULTS: Nineteen lesions in sixteen consecutive patients met the inclusion criteria. The median follow-up time was 39 months (range, 10-142) with 41 multiparametric MR-examinations in total. We found low values of N-acetyl-aspartate up to 1.5 cm from the target borders of SRS (P = 0.043) associated with high values of choline (P = 0.004) at the end of the observation period. Lactate levels in the adjacent tissue declined over time, whereas continuously high apparent-diffusion-coefficient values were noted (P < 0.001). CONCLUSION: Multiparametric MRI can depict radiobiological effects and their time course at a distance from the effectively treated site after SRS for brain metastases, even if conventional MRI findings are inconspicuous.

Levels of agreement between cardiac magnetic resonance and conductance catheter measurements of right ventricular volumes after pulmonary artery banding.

BACKGROUND: Pressure-volume analysis is the gold standard for quantifying pump function of the right ventricle (RV); however, volume measurements based on a conductive catheter may be imprecise. The reference method for volume assessment is cardiac magnetic resonance (CMR). PURPOSE: To determine the levels of agreement between RV volume measurements obtained by cine CMR, phase-contrast CMR (PC CMR), and a conductance catheter in an animal model. MATERIAL AND METHODS: CMR was performed in 20 sheep three months after pulmonary artery banding. Ejection fraction (EF), end-diastolic (EDV), end-systolic (ESV), and stroke volumes (SV) were obtained by cine CMR and conductance catheter. RESULTS: Statistically significant differences between cine CMR and conductance catheter derived volume measurements were found for EDV (P < 0.001), ESV (P < 0.05), and SV (P < 0.05). Bland-Altman analysis showed very poor agreement between the two methods: EDV, bias 36.27 mL, agreement of limits 1.96-70.57 mL; ESV, bias 15.33 mL, agreement of limits -6.89-37.55 mL; and SV, bias 20.69 mL, agreement of limits 8.01-49.10 mL. Good agreement was found for SV between cine CMR and PC CMR (bias -7.0 mL, agreement of limits -24.01-9.98 mL), while SV derived from PC CMR measurements showed poor agreement with conductance catheter (bias 27.76 mL, agreement of limits -3.84-59.26 mL). CONCLUSION: Poor agreement between the conductance catheter and CMR RV volume measurements was found. PC CMR and cine CMR measurements of SV agreed well.

Role of Counterions in Molecularly Imprinted Polymers for Anionic Species.

Small-molecule oxoanions are often imprinted noncovalently as carboxylates into molecularly imprinted polymers (MIPs), requiring the use of an organic counterion. Popular species are either pentamethylpiperidine (PMP) as a protonatable cation or tetraalkylammonium (TXA) ions as permanent cations. The present work explores the influence of the TXA as a function of their alkyl chain length, from methyl to octyl, using UV/vis absorption, fluorescence titrations, and HPLC as well as MD simulations. Protected phenylalanines (Z-l/d-Phe) served as templates/analytes. While the influence of the counterion on the complex stability constants and anion-induced spectral changes shows a monotonous trend with increasing alkyl chain length at the prepolymerization stage, the cross-imprinting/rebinding studies showed a unique pattern that suggested the presence of adaptive cavities in the MIP matrix, related to the concept of induced fit of enzyme-substrate interaction. Larger cavities formed in the presence of larger counterions can take up pairs of Z-x-Phe and smaller TXA, eventually escaping spectroscopic detection. Correlation of the experimental data with the MD simulations revealed that counterion mobility, the relative distances between the three partners, and the hydrogen bond lifetimes are more decisive for the response features observed than actual distances between interacting atoms in a complex or the orientation of binding moieties. TBA has been found to yield the highest imprinting factor, also showing a unique dual behavior regarding the interaction with template and fluorescent monomer. Finally, interesting differences between both enantiomers have been observed in both theory and experiment, suggesting true control of enantioselectivity. The contribution concludes with suggestions for translating the findings into actual MIP development.

Fluorescent monomers: "bricks" that make a molecularly imprinted polymer "bright".

Molecularly imprinted polymers (MIPs) are potent and established recognition phases in separation and enrichment applications. Because of their robustness, versatility and format adaptability, they also constitute very promising sensing phases, especially when the active sensing element is directly integrated into the MIP. Fluorescent MIPs incorporating fluorescent monomers are perhaps the best developed and most successful approach here. This article reviews the state of the art in this field, discussing the pros and cons of the use of fluorescent dye and probe derivatives as such monomers, the different molecular interaction forces for template complexation, signalling modes and a variety of related approaches that have been realized over the years, including Förster resonance energy transfer processes, covalent imprinting, postmodification attachment of fluorescent units and conjugated polymers as MIPs; other measurement schemes and sensing chemistries that use MIPs and fluorescence interrogation to solve analytical problems (fluorescent competitive assays, fluorescent analytes, etc.) are not covered here. Throughout the article, photophysical processes are discussed to facilitate understanding of the effects that can occur when one is planning for a fluorescence response to happen in a constrained polymer matrix. The article concludes with a concise assessment of the suitability of the different formats for sensor realization.

Incidental findings in computed tomographic angiography for planning percutaneous aortic valve replacement: advanced age, increased cancer prevalence?

BACKGROUND: Increased age is linked with a higher cancer risk according to model calculations. Patients with severe atherosclerotic aortic stenosis are of old age, therefore, a high incidence of malignancies should be found. PURPOSE: To evaluate the prevalence of clinically significant and potentially malignant incidental findings at computed tomographic angiography (CTA) performed in patients with severe aortic stenosis being assessed as to their suitability for transcatheter aortic valve replacement (TAVR). MATERIAL AND METHODS: Between August 2008 and April 2010, CTA of the thoraco-abdominal aorta and the pelvic arterial vessels was performed in 131 patients. There were 62 women (47%) and 69 men (53%); the mean age was 81.6 years (range, 64-91 years). Incidental findings were recorded and categorized as potentially malignant, clinically significant, and clinically insignificant. Clinically significant findings were defined as those requiring immediate therapy, intervention or imaging, or follow-up examination. RESULTS: Of the 131 study patients, 31 (23.7%) presented significant extravascular incidental findings, 19 (14.5%) in the thorax, and 12 (9.2%) in the abdomen. Five lesions (3.8%) were considered potentially malignant, three of them (2.3%) were new and highly suspicious for malignancies (two renal cell carcinomas and one hepatocellular carcinoma). In two patients (1.5%) mediastinal lymphadenopathy was found (recurrent malignant lymphoma und new metastases from known bladder cancer). CONCLUSION: The prevalence of highly suspicious malignant incidental findings in patients undergoing TAVR is 3.8% with an average age of 81.6 years which is not high compared to prevalence in the literature dealing with patients aged <70 years.

Effects of Tetrahydrolipstatin on Glioblastoma in Mice: MRI-Based Morphologic and Texture Analysis Correlated with Histopathology and Immunochemistry Findings-A Pilot Study.

BACKGROUND: This study aimed to investigate the effects of tetrahydrolipstatin (orlistat) on heterotopic glioblastoma in mice by applying MRI and correlating the results with histopathology and immunochemistry. METHODS: Human glioblastoma cells were injected subcutaneously into the groins of immunodeficient mice. After tumor growth of >150 mm3, the animals were assigned into a treatment group (n = 6), which received daily intraperitoneal injections of orlistat, and a control group (n = 7). MRI was performed at the time of randomization and before euthanizing the animals. Tumor volumes were calculated, and signal intensities were analyzed. The internal tumor structure was evaluated visually and with texture analysis. Western blotting and protein expression analysis were performed. RESULTS: At histology, all tumors showed high mitotic and proliferative activity (Ki67 ≥ 10%). Reduced fatty acid synthetase expression was measured in the orlistat group (p < 0.05). Based on the results of morphologic MRI-based analysis, tumor growth remained concentric in the control group and changed to eccentric in the treatment group (p < 0.05). The largest area under the receiver operating curve of the predictors derived from the texture analysis of T2w images was for wavelet transform parameters WavEnHL_s3 and WavEnLH_s4 at 0.96 and 1.00, respectively. CONCLUSIONS: Orlistat showed effects on heterotopically implanted glioblastoma multiforme in MRI studies of mice based on morphologic and texture analysis.

MRI for occult physeal fracture detection in children and adolescents.

BACKGROUND: Conventional radiography has limitations in the detection of physeal fractures before the closure of the physis occurs. Fracture detection may be improved by using magnetic resonance imaging (MRI). PURPOSE: To evaluate the usefulness of MRI for the detection of occult fractures involving the physis when radiography results are negative. MATERIAL AND METHODS: In this prospective study, 24 children (age range, 3-15 years; mean age, 10.7 years) received MRI if they met the following criteria: acute joint trauma, swelling and tenderness around the joint, limitations in bearing weight, an open physis, and negative radiography results for fractures. Fractures revealed by the MRI were classified according to the Salter-Harris classification system. Joint effusion, bone marrow edema, and periosteal alterations were graded on a three-point scale. The non-parametric Wilcoxon test and Fisher's exact test were used for the statistical evaluation. RESULTS: From a total of 24 MR data-sets, 23 were evaluated (one patient was excluded due to poor MR image quality). Elbow injuries were present in 10 patients (43.5%), distal tibia injuries in 10 patients (43.5%), and distal femur injuries in three patients (13%). MRI results excluded physeal fractures in 15 (65.2%) of the 23 children. An occult physeal fracture was detected with MRI in eight (34.8%) patients; of these, five (21.7%) had fractures of the elbow, two (8.7%) had fractures of the distal tibia, and one (4.3%) had a fracture of the distal femur. All of the patients with fractures and 11 of the 15 patients without fractures demonstrated bone marrow edema. CONCLUSION: The frequency of occult fracture, as detected by MRI, was 34.8%. Thus, MRI is a useful additional imaging method for the detection of occult fractures when radiography is negative.

Case report of a fulminant non-aneurysmal convexity subarachnoid hemorrhage after COVID-19.

We report on a case of a fulminant non-aneurysmal subarachnoid hemorrhage after COVID-19 in a patient without previous medical history or known previous illness despite a COVID-19 infection one month prior. We saw rarefied vessels in the area of the left middle cerebral artery besides a massive left frontal hemorrhage on cranial imaging. We concluded that these rarefied vessels are the expression of an RCVS, which fits the history of progressive headaches for one month. The RCVS might be caused by the COVID-19 infection and is related to the hemorrhage. Unfortunately, due to preoperative entrapment, brain death occurred a few days later.

The interior structure of breast microcalcifications assessed with micro computed tomography.

BACKGROUND: Morphology microcalcification descriptors help stratify the risk of breast malignancy. Micro CT is feasible for visualization of the fine-structure of tissues and may be suitible for high resolution microcalcification analysis. PURPOSE: To analyze the interior structure of microcalcifications using a micro CT imaging system. MATERIAL AND METHODS: Core needle breast biopsy specimens from 16 women with clustered microcalcifications were examined with micro CT. The samples measured between 0.8 to 1.2 mm in diameter. Micro CT scans with an isotropic voxel size of 8.4 µm were obtained to generate two- and three-dimensional images of the microcalcifications. The number of microcalcifications were counted on the magnified specimen radiogram and on micro CT. Attenuation values of microcalcifications were measured by drawing a region of interest (ROI) in the center of the microcalcifications. Two blinded observers assessed the morphology and the interior structure of microcalcifications. RESULTS: Five patients had benign and 11 patients had malignant breast lesions. On micro CT, microcalcifications of benign tissue showed a coarse lamellar or trabecular interior structure, whereas microcalcifications of breast cancer tissue showed a more uniform granular interior structure. There was no correlation between attenuation values of benign compared with malignant microcalcifications. CONCLUSION: On micro CT, an interior structure of microcalcifications is detectable. Benign and malignant microcalcifications display different patterns of interior structure.

Measuring performance status in pediatric patients with brain tumors--experience of the HIT-GBM-C protocol.

BACKGROUND: Measuring the quality of life or performance status in pediatric neurooncology has proven a challenge. Here, we report in a treatment protocol for pediatric patients with high-grade glioma and diffuse intrinsic pontine glioma. PROCEDURE: The Fertigkeitenskala Münster-Heidelberg (FMH) is a 56-item quantitative measure of health status. The number of yes answers is transformed to age-dependent percentiles. Physicians were also asked the patients' health status by their own judgment on a 1-5 scale: normal, mild handicap, age-normal activity severely reduced but patient not in bed, in bed, and in ICU. RESULTS: Assessments were available from 50 of 97 eligible patients. For 22 patients both questionnaire and the physicians score obtained. At the beginning of the treatment, only 5 patients scored over 40 FMH%, and 4 of these survived. Of 16 patients who initially scored less than 40 FMH%, 15 died. During later assessments, most FMH measures became gradually worse. FMH scores improved in three patients. The physician's judgment was documented at diagnosis and during treatment (n = 50). Per physician, 22% of the patients were normal before chemotherapy, decreasing to 16% in the middle of the protocol. At diagnosis only 16% of patients had severely reduced activity, which increased to 30.6% in the middle of the protocol. The FMH% correlated well with the physicians' judgments (P < 0.005). CONCLUSION: The FMH scale is easily obtained and provides a valid assessment of health status. Patients with poor performance at diagnosis had a poorer prognosis.

MGMT as a potential stratification marker in relapsed high-grade glioma of children: the HIT-GBM experience.

BACKGROUND: Studies in adults with malignant glioma suggest MGMT methylation as a stratification marker. Similar data for children are sparse. We investigated the impact of MGMT methylation and expression on survival of children with high-grade glioma (HGG) registered into the German HIT-GBM database receiving temozolomide (TMZ) as part of their treatment (n = 21 relapsed, n = 4 primary). PROCEDURE: Twenty-four patients were included retrospectively. Methylation specific PCR (MSP), calibrated combined bisulfite restriction analysis (COBRA), and immunohistochemistry (IHC) were applied. Survival analyses were performed by Kaplan-Meier and Cox proportional-hazards models. RESULTS: MSP demonstrated DNA methylation in 77%. Patients with a methylated MGMT promoter had a sixfold longer median EFS (P = 0.015; 5.5 months vs. 0.9 months). Considering the results of calibrated COBRA, MGMT methylation was again associated with an elevated EFS (P = 0.05; 10.2 months vs. 2.6 months) and OS (P = 0.06; 18.7 months vs. 7.2 months) only if methylation was >14%. No difference in EFS and OS at all was noted between unmethylated and tumors methylated at low level (n = 9). Twenty-two tumors were positive by IHC, 10 showed low MGMT expression (IHC score 0-4). We did not detect any difference in EFS and OS between moderate/high-expressing tumors (IHC score 6-12) and those with low or no expression (IHC score 0-4). CONCLUSION: DNA methylation, but not protein expression of MGMT was associated with an increased median EFS and OS of children with relapsed HGG. MGMT methylation status warrants prospective evaluation as a stratification marker for children with HGG.

Postoperative adjuvant dendritic cell-based immunotherapy in patients with relapsed glioblastoma multiforme.

PURPOSE: To investigate the therapeutic role of adjuvant vaccination with autologous mature dendritic cells (DC) loaded with tumor lysates derived from autologous, resected glioblastoma multiforme (GBM) at time of relapse. EXPERIMENTAL DESIGN: Fifty-six patients with relapsed GBM (WHO grade IV) were treated with at least three vaccinations. Children and adults were treated similarly in three consecutive cohorts, with progressively shorter vaccination intervals per cohort. Feasibility and toxicity were assessed as well as effect of age, extent of resection, Karnofsky Performance Score, and treatment cohort on the progression-free (PFS) and overall survival (OS) using univariable and multivariable analysis. RESULTS: Since the prevaccine reoperation, the median PFS and OS of the total group was 3 and 9.6 months, respectively, with a 2-year OS of 14.8%. Total resection was a predictor for better PFS both in univariable analysis and after correction for the other covariates. For OS, younger age and total resection were predictors of a better outcome in univariable analysis but not in multivariable analysis. A trend to improved PFS was observed in favor of the faster DC vaccination schedule with tumor lysate boosting. Vaccine-related edema in one patient with gross residual disease before vaccination was the only serious adverse event. CONCLUSION: Adjuvant DC-based immunotherapy for patients with relapsed GBM is safe and can induce long-term survival. A trend to PFS improvement was shown in the faster vaccination schedule. The importance of age and a minimal residual disease status at the start of the vaccination is underscored.

Right Ventricular Function After Pulmonary Artery Banding: Adaptive Processes Assessed by CMR and Conductance Catheter Measurements in Sheep.

This experimental study describes the adaptive processes of the right ventricular (RV) myocardium after pulmonary artery banding (PAB) evaluated by cine cardiac magnetic resonance (CMR), phase-contrast CMR (PC-CMR), and conductance catheter. Seven sheep were subjected to CMR 3 months after PAB. Conductance catheter measurements were performed before and 3 months after PAB. Four nonoperated, healthy, age-matched animals served as controls. Higher RV masses (p < 0.01), elevated RV end-systolic volumes (p < 0.05), and lower RV ejection fraction (p < 0.01) were observed in the operated group. The time-to-peak pulmonary artery flow was longer in the banding group (p < 0.01). RV maximal pressure and RV end-diastolic pressure correlated with the time-to-peak flow in the pulmonary artery (r = - 0.70 and - 0.69, respectively). In summary, PAB caused RV hypertrophy, increased myocardial contractility, and decreased RV-EF and cardiac output. The time-to-peak pulmonary artery flow correlated with RV pressures.

An automated and parallelised DIY-dosing unit for individual and complex feeding profiles: Construction, validation and applications.

Since biotechnological research becomes more and more important for industrial applications, there is an increasing need for scalable and controllable laboratory procedures. A widely used approach in biotechnological research to improve the performance of a process is to vary the growth rates in order to find the right balance between growth and the production. This can be achieved by the application of a suitable feeding strategy. During this initial bioprocess development, it is beneficial to have at hand cheap and easy setups that work in parallel (e.g. in shaking flasks). Unfortunately, there is a gap between these easy setups and defined and controllable processes, which are necessary for up-scaling to an industrial relevant volume. One prerequisite to test and evaluate different process strategies apart from batch-mode is the availability of pump systems that allow for defined feeding profiles in shaking flasks. To our knowledge, there is no suitable dosing device on the market which fulfils the requirements of being cheap, precise, programmable, and parallelizable. Commercially available dosing units are either already integrated in bioreactors and therefore inflexible, or not programmable, or expensive, or a combination of those. Here, we present a LEGO-MINDSTORMS-based syringe pump, which has the potential of being widely used in daily laboratory routine due to its low price, programmability, and parallelisability. The acquisition costs do not exceed 350 € for up to four dosing units, that are independently controllable with one EV3 block. The system covers flow rates ranging from 0.7 µL min-1 up to 210 mL min-1 with a reliable flux. One dosing unit can convey at maximum a volume of 20 mL (using all 4 units even up to 80 mL in total) over the whole process time. The design of the dosing unit enables the user to perform experiments with up to four different growth rates in parallel (each measured in triplicates) per EV3-block used. We estimate, that the LEGO-MINDSTORMS-based dosing unit with 12 syringes in parallel is reducing the costs up to 50-fold compared to a trivial version of a commercial pump system (~1500 €) which fits the same requirements. Using the pump, we set the growth rates of a E. coli HMS174/DE3 culture to values between 0.1 and 0.4 h-1 with a standard deviation of at best 0.35% and an average discrepancy of 13.2%. Additionally, we determined the energy demand of a culture for the maintenance of the pTRA-51hd plasmid by quantifying the changes in biomass yield with different growth rates set. Around 25% of total substrate taken up is used for plasmid maintenance. To present possible applications and show the flexibility of the system, we applied a constant feed to perform microencapsulation of Pseudomonas putida and an individual dosing profile for the purification of a his-tagged eGFP via IMAC. This smart and versatile dosing unit, which is ready-to-use without any prior knowledge in electronics and control, is affordable for everyone and due to its flexibility and broad application range a valuable addition to the laboratory routine.

Cerebral MRI lesions and anti-tumor necrosis factor-alpha therapy.

We discuss two cases receiving different anti-tumornecrosis-factor alpha antagonists (anti-TNF-alpha); one for psoriatic arthritis (PA) and the other for ankylosing spondylitis (AS). Due to neurological symptoms cerebral magnetic resonance imaging (MRI) was performed and cerebral lesions were detected. Our interpretations of these cerebral lesions and the resulting diagnostic and therapeutic consequences are presented in regard of data published in the medical literature.

pTRA - A reporter system for monitoring the intracellular dynamics of gene expression.

The presence of standardised tools and methods to measure and represent accurately biological parts and functions is a prerequisite for successful metabolic engineering and crucial to understand and predict the behaviour of synthetic genetic circuits. Many synthetic gene networks are based on transcriptional circuits, thus information on transcriptional and translational activity is important for understanding and fine-tuning the synthetic function. To this end, we have developed a toolkit to analyse systematically the transcriptional and translational activity of a specific synthetic part in vivo. It is based on the plasmid pTRA and allows the assignment of specific transcriptional and translational outputs to the gene(s) of interest (GOI) and to compare different genetic setups. By this, the optimal combination of transcriptional strength and translational activity can be identified. The design is tested in a case study using the gene encoding the fluorescent mCherry protein as GOI. We show the intracellular dynamics of mRNA and protein formation and discuss the potential and shortcomings of the pTRA plasmid.

Integrating fluorescent molecularly imprinted polymer (MIP) sensor particles with a modular microfluidic platform for nanomolar small-molecule detection directly in aqueous samples.

Fluorescent sensory MIP (molecularly imprinted polymer) particles were combined with a droplet-based 3D microfluidic system for the selective determination of a prototype small-molecule analyte of environmental concern, 2,4-dichlorophenoxyacetic acid or 2,4-D, at nanomolar concentration directly in water samples. A tailor-made fluorescent indicator cross-linker was thus designed that translates the binding event directly into an enhanced fluorescence signal. The phenoxazinone-type cross-linker was co-polymerized into a thin MIP layer grafted from the surface of silica microparticles following a RAFT (reversible addition-fragmentation chain transfer) polymerization protocol. While the indicator cross-linker outperformed its corresponding monomer twin, establishment of a phase-transfer protocol was essential to guarantee that the hydrogen bond-mediated signalling mechanism between the urea binding site on the indicator cross-linker and the carboxylate group of the analyte was still operative upon real sample analysis. The latter was achieved by integration of the fluorescent core-shell MIP sensor particles into a modular microfluidic platform that allows for an in-line phase-transfer assay, extracting the analyte from aqueous sample droplets into the organic phase that contains the sensor particles. Real-time fluorescence determination of 2,4-D down to 20nM was realized with the system and applied for the analysis of various surface water samples collected from different parts of the world.

IL-2 and autoimmune disease.

A decade after the first description of IL-2-deficient mice, the redundancy of IL-2 as a T cell growth factor is well accepted and the focus of research has shifted to the unexpected multiorgan autoimmunity and inflammation observed in mice lacking components of the IL-2/IL-2R system. So far, a set of defects at the levels of repertoire selection, the generation of suppressive regulatory T cells, T cell homing and clonal contraction via activation induced cell death (AICD) have been documented. We propose that these individual defects jointly contribute to the severe disturbance of T cell homeostasis and self-tolerance underlying the immunopathology of the IL-2 deficiency syndrome.

Radiation injury versus malignancy after stereotactic radiosurgery for brain metastases: impact of time-dependent changes in lesion morphology on MRI.

Background: We sought to determine whether radiation-induced injuries could be distinguished from malignancy after stereotactic radiosurgery (SRS) by analyzing time-dependent changes in lesion morphology on sequential MRI for up to 55min. Methods: In 31 consecutive patients treated with SRS for brain metastases, the time-dependent changes in lesion morphology were analyzed on MRI 2min, 15min, and 55min after contrast administration and on subtraction images. A simultaneous, matched-pairs approach was used for quantitative region of interest analysis of the area of the lesion. Qualitative analysis comprised the shape of the border, the structure of the interior area, the presence of leptomeningeal enhancement, and feeding vessels. The signal intensity changes of the border and the interior area of the lesions over time were assessed visually. The time-dependent changes in the 2 entities were compared. Results: Twenty radiation-induced injuries and 21 malignancies were analyzed. A significant interaction effect between time point and diagnosis (P<.001) was found for the time-dependent changes of the margin of the lesion for 2min to 15min and in signal intensity differences of the rim and interior area as well as of the size of the interior area for up to 55min. All radiation-induced injuries showed a black interior area on the subtraction images for 15min minus 55min, whereas all malignant lesions had white components (P<.001). Conclusions: Analysis of time-dependent changes in lesion morphology on sequential MRI for up to 55min is a reliable tool to distinguish radiation-induced injuries from malignancy after SRS.