Novel Noninvasive Paraclinical Study Method for Investigation of Liver Diseases.

Based on a prior university patent, the authors developed a novel type of bioimpedance-based test method to noninvasively detect nonalcoholic fatty liver disease (NAFLD). The development of a new potential NAFLD diagnostic procedure may help to understand the underlying mechanisms between NAFLD and severe liver diseases with a painless and easy-to-use paraclinical examination method, including the additional function to detect even the earlier stages of liver disease. The aim of this study is to present new results and the experiences gathered in relation to NAFLD progress during animal model and human clinical trials.

Deconvolution Analysis of the Non-Ionic Iomeprol, Iobitridol and Iodixanol Contrast Media-Treated Human Whole Blood Thermograms: A Comparative Study.

To study the effect of non-ionic contrast media on anticoagulated and non-anticoagulated human whole blood samples, calorimetric measurements were performed. The anticoagulated plasma showed the greatest fall in the total ΔH after Iodixanol treatment. The plasma-free erythrocytes revealed a pronounced shift in the Tmax and a decrease in the ΔH of hemoglobin and transferrin. The total ΔH of Iodixanol treatment showed the highest decline, while Iomeprol and Iobitridol had fewer adverse effects. Similarly, the non-anticoagulated samples revealed a decrease both in the Tmax and the ΔH of albumin and immunoglobulin-specific transitions. The total ΔH showed that Iodixanol had more influence on the serum. The serum-free erythrocyte samples resulted in a significant drop in the Tmax of erythrocyte and transferrin (~5-6 °C). The ΔH of deconvolved hemoglobin and transferrin decreased considerably; however, the ΔH of albumin increased. Surprisingly, compared to Iomeprol and Iobitridol treatments, the total ΔH of Iodixanol was less pronounced in the non-anticoagulated erythrocyte samples. In sum, each non-ionic contrast medium affected the thermal stability of anticoagulated and non-anticoagulated erythrocyte proteins. Interestingly, Iodixanol treatment caused more significant effects. These findings suggest that conformational changes in blood components can occur, which can potentially lead to the increased prevalence of cardiovascular dysfunctions and blood clotting.

Optimal Renal Artery-Aorta Angulation Revealed by Flow Simulation.

INTRODUCTION: In the circulatory system, the vessel branching angle may have hemodynamic consequences. We hypothesized that there is a hemodynamically optimal range for the renal artery's branching angle. METHODS: Data on the posttransplant kinetics of estimated glomerular filtration rate (eGFR) were analyzed according to the donor and implant sides (right-to-right and left-to-right position; n = 46). The renal artery branching angle from the aorta of a randomly selected population was measured using an X-ray angiogram (n = 44). Computational fluid dynamics simulation was used to elucidate the hemodynamic effects of angulation. RESULTS AND DISCUSSION: Renal transplant patients receiving a right donor kidney to the right side showed faster adaptation and higher eGFR values than those receiving a left donor kidney to the right side (eGFR: 65 ± 7 vs. 56 ± 6 mL/min/1.73 m2; p < 0.01). The average branching angle on the left side was 78° and that on the right side was 66°. Simulation results showed that the pressure, volume flow, and velocity were relatively constant between 58° and 88°, indicating that this range is optimal for the kidneys. The turbulent kinetic energy does not change significantly between 58° and 78°. CONCLUSION: The results suggest that there is an optimal range for the renal artery's branching angle from the aorta where hemodynamic vulnerability caused by the degree of angulation is the lowest, which should be considered during kidney transplantations.

New computational fluid dynamics-based method for morphological and functional assessment in cardiovascular skill training.

Objective: During cardiovascular surgical skill training, the direct quantification regarding surgical performance is still lacking, including transferring clinically relevant information. Methods: We introduced a novel computational fluid dynamics-based method in support of vascular surgical hands-on training, which applies continuous self-assessment in vascular anastomoses. The validation of the methodology was implemented in comparing with conventional training courses. Results: The fifth and seventh consecutive anastomoses of the experimental group showed significantly improved results regarding anastomosis quality when compared with the control group. Conclusions: Consecutive demonstration of three-dimensional morphology and functional assessment of anastomoses results in improved practical performance among learners regarding anastomosis quality.

[Participation indicators of organized mammography screening in Hungary between 2012-2021]. / A szervezett lakossági mammográfiás emloszurés részvételi mutatói 2012­2021 között Magyarországon.

The aim of our study is to analyze the participation indicators of screening rounds Nr. 6-10 (2012-2021) of the organized nationwide mammography screening program. Data derived from the nationwide financing database of the Hungarian National Health Insurance Fund Management and covered the period 2012-2021. We analyzed both diagnostic and screening mammography examinations. Between 2012 and 2019 the coverage (screening and diagnostic mammography) varied between 48.1-51.5, which decreased to 31.8% in 2020-2021. Within total coverage, the organized screening rate declined from 30.3-31.2 to 20.0, while the diagnostic mammography rate decreased from 17.7-20.7% to 11.8%. We can conclude that the number of both the diagnostic and screening mammography declined. In order to reduce the mortality of breast cancer, participation rate of mammography screening program should be increased.

Plasma Levels and Renal Handling of Amino Acids Contribute to Determination of Risk of Mortality or Feed of Ventilation in Patients with COVID-19.

COVID-19 infection may lead to serious complications, e.g., need for mechanical ventilation or death in some cases. A retrospective analysis of patients referred to our COVID Emergency Department, indiscriminately, was performed. A routine lab analysis measured amino acids in plasma and urine of patients. Data of surviving and deceased patients and those requiring or not requiring mechanical ventilation were compared, and logistic regression analyses have been performed. Deceased patients were older, had higher blood glucose, potassium, AST, LDH, troponin, d-dimer, hsCRP, procalcitonin, interleukin-6 levels (p < 0.05 for all). They had lower plasma serine, glycine, threonine, tryptophan levels (p < 0.01), higher tyrosine and phenylalanine levels (p < 0.05), and higher fractional excretion of arginine, methionine, and proline (p < 0.05) than survivors. In a regression model, age, severity score of COVID-pneumonia, plasma levels of threonine and phenylalanine were predictors of in-hospital mortality. There was a difference in ventilated vs. non-ventilated patients in CT-scores, glucose, and renal function (p < 0.001). Using logistic regression, CT-score, troponin, plasma level, and fractional excretion of glycine were predictors of ventilation. Plasma levels and renal excretion of certain amino acids are associated with the outcome of COVID-19 infection beside other parameters such as the CT-score or age.

Cerebral Microbleeds May Be Less Detectable by Susceptibility Weighted Imaging MRI From 24 to 72 Hours After Traumatic Brain Injury.

Purpose: A former rodent study showed that cerebral traumatic microbleeds (TMBs) may temporarily become invisible shortly after injury when detected by susceptibility weighted imaging (SWI). The present study aims to validate this phenomenon in human SWI. Methods: In this retrospective study, 46 traumatic brain injury (TBI) patients in various forms of severity were included and willingly complied with our strict selection criteria. Clinical parameters potentially affecting TMB count, Rotterdam and Marshall CT score, Mayo Clinic Classification, contusion number, and total volume were registered. The precise time between trauma and MRI [5 h 19 min to 141 h 54 min, including SWI and fluid-attenuated inversion recovery (FLAIR)] was individually recorded; TMB and FLAIR lesion counts were assessed. Four groups were created based on elapsed time between the trauma and MRI: 0-24, 24-48, 48-72, and >72 h. Kruskal-Wallis, ANOVA, Chi-square, and Fisher's exact tests were used to reveal differences among the groups within clinical and imaging parameters; statistical power was calculated retrospectively for each comparison. Results: The Kruskal-Wallis ANOVA with Conover post hoc analysis showed significant (p = 0.01; 1-ß > 0.9) median TMB number differences in the subacute period: 0-24 h = 4.00 (n = 11); 24-48 h = 1 (n = 14); 48-72 h = 1 (n = 11); and 72 h ≤ 7.5 (n = 10). Neither clinical parameters nor FLAIR lesions depicted significant differences among the groups. Conclusion: Our results demonstrate that TMBs on SWI MRI may temporarily become less detectable at 24-72 h following TBI.

Muscle damage in response to a single bout of high intensity concentric exercise in patients with Pompe disease.

BACKGROUND: In Pompe disease, resistance exercise could be an effective treatment to delay motor function impairment, however, the acute effects of this exercise modality are unclear. METHODS: In a prospective cohort study, we compared responses to a single bout of resistance exercise by serum markers of muscle damage and quantitative muscle magnetic resonance imaging (MRI) in patients (n=12) and age- and gender-matched healthy controls (n=12). Participants performed 50 maximal effort concentric knee flexions on a dynamometer. RESULTS: Twenty-four hours after exercise, levels of serum creatine kinase, lactate dehydrogenase and myoglobin increased in controls. In contrast, only myoglobin level increased in patients. All elevated serum markers declined by 48 hours after exercise in both groups. Mild soreness developed at 24 hours, which disappeared at 48 hours in both groups. In controls, MRI R2* relaxation rate reduced immediately and 24 hours after exercise, indicating increased water content and muscle perfusion. In patients, exercise had no effect on R2* values. The resistance exercise did not induce acute strength deficit in patients, rather, patients increased their strength by 24 hours. When serum marker changes were normalized to the magnitude of knee flexor tension developed during exercise, lactate dehydrogenase response was greater in patients. CONCLUSIONS: Late-onset Pompe disease did not exacerbate exercise-induced muscle damage, however, lactate dehydrogenase may be monitored to screen high responders during high intensity resistance exercise interventions.

Teleradiology-based stroke network in Western and Southern Transdanubia in Hungary / Stroke-ellátást támogató teleradiológiai hálózat a Nyugat- és Dél-Dunántúlon.

Összefoglaló. Bevezetés: A stroke kezelésének lehetoségei az utóbbi években jelentosen megváltoztak: a thrombolysis után bevezetésre került a mechanikus thrombectomia, és a terápiás idoablak is jelentosen kitágult az utóbbi évek nagy multicentrikus tanulmányai alapján. Ezek a lehetoségek új igényeket fogalmaztak meg a képalkotó diagnosztikával szemben: az ischaemia okozta morfológiai elváltozások mellett az artériás és a kollaterális rendszer állapotát, valamint bizonyos esetekben az agy szöveti perfúzióját is szükséges meghatározni. Ezeket a komplex kiértékelési feladatokat ma már mesterségesintelligencia-algoritmusok támogathatják, melyek a kiértékelést pár perc alatt elvégezve segítenek a terápiás döntés kialakításában. Célkituzés: A Dél- és a Nyugat-dunántúli régióban hat intézmény részvételével egy dedikált stroke teleradiológiai hálózat kialakítása. Módszer: A stroke-CT-kiértékelo szoftver és a képkommunikáció integrációja, a vizsgálati protokollok technikai paramétereinek egységesítése, a kiértékelési eredmények teleradiológiai megjelenítése valósult meg a hálózat kialakítása során. Eredmények: A hálózat egységesítette nemcsak a stroke-CT-protokollok beállításait, de beutalási és értékelési szempontjait is. A stroke-CT-kiértékelések és a mechanikus thrombectomiák száma is emelkedett az elmúlt egy évben. Következtetés: A dedikált teleradiológiai stroke-hálózat segítségével optimalizálni kívánjuk a régió stroke-ellátását: egyrészt lehetoleg ne maradjanak ellátatlanul a thrombectomiából valószínuleg profitáló betegek, másrészt ne terheljük az ellátórendszert olyan esetekkel, melyekrol a teljes dokumentáció ismeretében derül ki, hogy nem javasolt a beavatkozás. Orv Hetil. 2021; 162(17): 668-675. INTRODUCTION: The possibilities of cerebral stroke management have changed substantially during the last few years. Following a few multicentric studies, mechanical thrombectomy became an established method besides thrombolysis. In addition, the therapeutic window for both methods is much wider now than before. These changes described above demanded more information of CT morphological changes due to ischemia, but the condition and functionality of the arterial and collateral system, and occasionally tissue perfusion performance should also be characterized. Recently, evaluation of different computer tomographic (CT) measurements can be done using artificial intelligence based methods, which perform data analysis in a few minutes. OBJECTIVE: To establish a dedicated stroke teleradiology network with artificial intelligence based image analysis in Western and Southern Transdanubia in Hungary that involves six partner institutes. METHOD: Integration of automated image analysis with teleradiology software was established, and the technical parameters of examination protocols were unified. Results of stroke CT image analysis became accessible through the teleradiology network. RESULTS: The daily use of integrated central image analysis and image communication had a positive impact on referrals and therapeutic evaluation of stroke cases. The number of image processing and mechanical thrombectomy increased during the last year. CONCLUSION: With the help of the dedicated teleradiology stroke network, we want to optimize the stroke care in the region: on the one hand, patients who are likely to benefit from thrombectomy should not be left unattended, on the other, the health care system should not be burdened with cases, when intervention is not recommended having the complete clinical data accessed. Orv Hetil. 2021; 162(17): 668-675.

Microbleeds show a characteristic distribution in cerebral fat embolism.

This systematic review aims to test the hypothesis that microbleeds detected by MRI are common and show a characteristic pattern in cerebral fat embolism (CFE). Eighty-four papers involving 140 CFE patients were eligible for this review based on a systematic literature search up to 31 January 2020. An additional case was added from hospital records. Patient data were individually scrutinised to extract epidemiological, clinical and imaging variables. Characteristic CFE microbleed pattern resembling a "walnut kernel" was defined as punctuate hypointensities of monotonous size, diffusely located in the subcortical white matter, the internal capsule and the corpus callosum, with mostly spared corona radiata and non-subcortical centrum semiovale, detected by susceptibility- or T2* weighted imaging. The presence rate of this pattern and other, previously described MRI markers of CFE such as the starfield pattern and further diffusion abnormalities were recorded and statistically compared. The presence rate of microbleeds of any pattern, the "walnut kernel microbleed pattern", diffusion abnormality of any pattern, the starfield pattern, and cytotoxic edema in the corpus callosum was found to be 98.11%, 89.74%, 97.64%, 68.5%, and 77.27% respectively. The presence rate between the walnut kernel and the starfield pattern was significantly (p < 0.05) different. Microbleeds are common and mostly occur in a characteristic pattern resembling a "walnut kernel" in the CFE MRI literature. Microbleeds of this pattern in SWI or T2* MRI, along with the starfield pattern in diffusion imaging appear to be the most important imaging markers of CFE and may aid the diagnosis in clinically equivocal cases.

False-Positive Malignant Diagnosis of Nodule Mimicking Lesions by Computer-Aided Thyroid Nodule Analysis in Clinical Ultrasonography Practice.

This study aims to test computer-aided diagnosis (CAD) for thyroid nodules in clinical ultrasonography (US) practice with a focus towards identifying thyroid entities associated with CAD system misdiagnoses. Two-hundred patients referred to thyroid US were prospectively enrolled. An experienced radiologist evaluated the thyroid nodules and saved axial images for further offline blinded analysis using a commercially available CAD system. To represent clinical practice, not only true nodules, but mimicking lesions were also included. Fine needle aspiration biopsy (FNAB) was performed according to present guidelines. US features and thyroid entities significantly associated with CAD system misdiagnosis were identified along with the diagnostic accuracy of the radiologist and the CAD system. Diagnostic specificity regarding the radiologist was significantly (p < 0.05) higher than when compared with the CAD system (88.1% vs. 40.5%) while no significant difference was found in the sensitivity (88.6% vs. 80%). Focal inhomogeneities and true nodules in thyroiditis, nodules with coarse calcification and inspissated colloid cystic nodules were significantly (p < 0.05) associated with CAD system misdiagnosis as false-positives. The commercially available CAD system is promising when used to exclude thyroid malignancies, however, it currently may not be able to reduce unnecessary FNABs, mainly due to the false-positive diagnoses of nodule mimicking lesions.

Benefits of respiratory navigation aided MRI in case of large abdominal tumors of canines: A case study.

Magnetic resonance imaging using respiratory navigation technique can be the number one diagnostic method determining operability of large-sized abdominal tumors of dogs. This technique eliminates motion artifacts and makes possible the visualization of the origin and extent of the tumor and of the possible abdominal metastases.

Cerebral Microbleeds Temporarily Become Less Visible or Invisible in Acute Susceptibility Weighted Magnetic Resonance Imaging: A Rat Study.

Previously, we reported human traumatic brain injury cases demonstrating acute to subacute microbleed appearance changes in susceptibility-weighted imaging (SWI-magnetic resonance imaging [MRI]). This study aims to confirm and characterize such temporal microbleed appearance alterations in an experimental model. To elicit microbleed formation, brains of male Sprague Dawley rats were pierced in a depth of 4 mm, in a parasagittal position bilaterally using 159 µm and 474 µm needles, without the injection of autologous blood or any agent. Rats underwent 4.7 T MRI immediately, then at multiple time points until 125 h. Volumes of hypointensities consistent with microbleeds in SWI were measured using an intensity threshold-based approach. Microbleed volumes across time points were compared using repeated measures analysis of variance. Microbleeds were assessed by Prussian blue histology at different time points. Hypointensity volumes referring to microbleeds were significantly decreased (corrected p < 0.05) at 24 h compared with the immediate or the 125 h time points. By visual inspection, microbleeds were similarly detectable at the immediate and 125 h imaging but were decreased in extent or completely absent at 24 h or 48 h. Histology confirmed the presence of microbleeds at all time points and in all animals. This study confirmed a general temporary reduction in visibility of microbleeds in the acute phase in SWI. Such short-term appearance dynamics of microbleeds should be considered when using SWI as a diagnostic tool for microbleeds in traumatic brain injury and various diseases.

Both hemorrhagic and non-hemorrhagic traumatic MRI lesions are associated with the microstructural damage of the normal appearing white matter.

Traumatic microbleeds (TMBs) and non-hemorrhagic lesions (NHLs) on MRI are regarded as surrogate markers of diffuse axonal injury. However, the actual relation between lesional and diffuse pathology remained unclear, since lesions were related to clinical parameters, largely influenced by extracranial factors. The aim of this study is to directly compare TMBs, NHLs and their regional features with the co-existing diffuse injury of the normal appearing white matter (NAWM) as measured by diffusion tensor imaging (DTI). Thirty-eight adults with a closed traumatic brain injury (12 mild, 4 moderate and 22 severe) who underwent susceptibility weighted imaging (SWI), T1-, T2 weighted and FLAIR MRI and routine CT were included in the study. TMB (on SWI) and NHL (on T1-, T2 weighted and FLAIR images) features and Rotterdam scores were evaluated. DTI metrics such as fractional anisotropy (FA) and mean diffusivity (MD) were measured over different NAWM regions. Clinical parameters including age; Glasgow Coma Scale; Rotterdam score; TMB and NHL features were correlated to regional NAWM diffusivity using multiple regression. Overall NHL presence and basal ganglia area TMB load were significantly, negatively correlated with the subcortical NAWM FA values (partial r=-0.37 and -0.36; p=0.006 and 0.025, respectively). The presence of any NHL, or TMBs located in the basal ganglia area indicates diffuse NAWM damage even after adjusting for clinical and CT parameters. To estimate DAI, a conventional lesional MRI pathology evaluation might at least in part substitute the use of quantitative DTI, which is yet not widely feasible in a clinical setting.

Quantitative comparison of delayed ferumoxytol T1 enhancement with immediate gadoteridol enhancement in high grade gliomas.

PURPOSE: Delayed ferumoxytol enhancement on T1 -weighted images appears visually similar to gadoteridol enhancement. The purpose of this study was to quantitatively compare ferumoxytol T1 enhancement to gadoteridol enhancement with an objective, semi-automated method. METHODS: 206 sets of post-gadoteridol and 24 h post-ferumoxytol T1 -weighted scans from 58 high grade glioma patients were analyzed (9 pre-chemoradiation, 111 < 90 days post-chemoradiation, 21 > 90 days post-chemoradiation, 65 post-bevacizumab scans). Enhancement volumes and signal intensities normalized to normal appearing tissue proximal to enhancement were calculated with a semi-automated method. Enhancement cube root volumes (D) and signal intensities (SI) were compared between the 2 contrast agents, and relative difference of D and SI were compared in different treatment groups with multivariate analysis. Within patient differences in D and SI before and after treatment with bevacizumab or steroid were assessed in 26 patients in each treatment group. RESULTS: When compared to gadoteridol, ferumoxytol D was 13.83% smaller and SI was 7.24% lower (P < 0.0001). The relative differences in D and SI between the 2 contrast agents were not significantly different between treatment groups (P > 0.05). Relative difference in D and SI did not change significantly in response to bevacizumab (P = 0.5234 and P = 0.2442, respectively) or to steroid (P = 0.3774, P = 0.0741) in the within patient comparison. CONCLUSION: The correlation between the 2 contrast agents' enhancement size and signal intensity and their similar behavior in response to therapy suggest that ferumoxytol can be used for revealing enhancement in high grade glioma patients. Magn Reson Med 80:224-230, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Comparison of accuracy between FSL's FIRST and Freesurfer for caudate nucleus and putamen segmentation.

Although several methods have been developed to automatically delineate subcortical gray matter structures from MR images, the accuracy of these algorithms has not been comprehensively examined. Most of earlier studies focused primarily on the hippocampus. Here, we assessed the accuracy of two widely used non-commercial programs (FSL-FIRST and Freesurfer) for segmenting the caudate and putamen. T1-weighted 1 mm3 isotropic resolution MR images were acquired for thirty healthy subjects (15 females). Caudate nucleus and putamen were segmented manually by two independent observers and automatically by FIRST and Freesurfer (v4.5 and v5.3). Utilizing manual labels as reference standard the following measures were studied: Dice coefficient (D), percentage volume difference (PVD), absolute volume difference as well as intraclass correlation coefficient (ICC) for consistency and absolute agreement. For putamen segmentation, FIRST achieved higher D, lower PVD and higher ICC for absolute agreement with manual tracing than either version of Freesurfer. Freesurfer overestimated the putamen, while FIRST was not statistically different from manual tracing. The ICC for consistency with manual tracing was similar between the two methods. For caudate segmentation, FIRST and Freesurfer performed more similarly. In conclusion, Freesurfer and FIRST are not equivalent when comparing to manual tracing. FIRST was superior for putaminal segmentation.

Age at onset and seizure frequency affect white matter diffusion coefficient in patients with mesial temporal lobe epilepsy.

In mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), structural abnormalities are present not only in the hippocampus but also in the white matter with ipsilateral predominance. Although the timing of epilepsy onset is commonly associated with clinical and semiological dissimilarities, limited data exist regarding white matter diffusion changes with respect to age at epilepsy onset. The aim of this study was to investigate diffusion changes in the white matter of patients with unilateral MTLE-HS with respect to clinical parameters and to compare them with an age- and sex-matched healthy control group. Apparent diffusion coefficients (ADCs) were derived using monoexponential approaches from 22 (11 early and 11 late age at onset) patients with unilateral MTLE-HS and 22 age- and sex-matched control subjects after acquiring diffusion-weighted images on a 3T MRI system. Data were analyzed using two-tailed t-tests and multiple linear regression models. In the group with early onset MTLE-HS, ADC was significantly elevated in the ipsilateral hemispheric (p=0.04) and temporal lobe white matter (p=0.01) compared with that in controls. These differences were not detectable in late onset MTLE-HS patients. Apparent diffusion coefficient of the group with early onset MTLE-HS was negatively related to age at epilepsy onset in the ipsilateral hemispheric white matter (p=0.03) and the uncinate fasciculus (p=0.03), while in patients with late onset MTLE-HS, ADC was no longer dependent on age at epilepsy onset itself but rather on the seizure frequency in the ipsilateral uncinate fasciculus (p=0.03). Such diffusivity pattern has been associated with chronic white matter degeneration, reflecting myelin loss and higher extracellular volume which are more pronounced in the frontotemporal regions and also depend on clinical features. In the group with early onset MTLE-HS, the timing of epilepsy seems to be the major cause of white matter abnormalities while in late onset disease, it has a secondary role in provoking diffusion changes.

Timed, sequential administration of paclitaxel improves its cytotoxic effectiveness in a cell culture model.

Paclitaxel (taxol) is a chemotherapeutic agent frequently used in combination with other anti-neoplastic drugs. It is most effective during the M phase of the cell-cycle and tends to cause synchronization in malignant cells lines. In this study, we investigated whether timed, sequential treatment based on the cell-cycle characteristics could be exploited to enhance the cytotoxic effect of paclitaxel. We characterized the cell-cycle properties of a rapidly multiplying cell line (Sp2, mouse myeloma cells) by propidium-iodide DNA staining such as the lengths of various cell cycle phases and population duplication time. Based on this we designed a paclitaxel treatment protocol that comprised a primary and a secondary, timed treatment. We found that the first paclitaxel treatment synchronized the cells at the G2/M phase but releasing the block by stopping the treatment allowed a large number of cells to enter the next cell-cycle by a synchronized manner. The second treatment was most effective during the time when these cells approached the next G2/M phase and was least effective when it occurred after the peak time of this next G2/M phase. Moreover, we found that after mixing Sp2 cells with another, significantly slower multiplying cell type (Jurkat human T-cell leukemia) at an initial ratio of 1:1, the ratio of the two different cell types could be influenced by timed sequential paclitaxel treatment at will. Our results demonstrate that knowledge of the cell-cycle parameters of a specific malignant cell type could improve the effectivity of the chemotherapy. Implementing timed chemotherapeutic treatments could increase the cytotoxicity on the malignant cells but also decrease the side-effects since other, non-malignant cell types will have different cell-cycle characteristic and be out of synch during the treatment.

In vivo detection of hyperacute neuronal compaction and recovery by MRI following electric trauma in rats.

PURPOSE: To verify the following phenomenon in vivo using quantitative magnetic resonance imaging (MRI). Neuronal compression may occur following brain injuries in the cortex and hippocampus. As well being characterized by previous histological studies in rats, the majority of these neurons undergo hyperacute recovery rather than apoptotic death. MATERIALS AND METHODS: Twenty male Wistar rats were assigned into injured or sham-injured groups (n = 10). The injured group underwent an electric trauma model to provoke compacted neuron formation. A T1 map was acquired prior to the injury and 10 T1 maps were acquired consecutively over a period of 2.5 hours after the injury, using a 3.0T scanner. Voxelwise statistical analyses were performed between timepoints. To enable comparison with the histological appearance of the compacted neurons, silver staining was performed on a sham-injured rat and five injured rats, 10, 40, 90, 150, and 300 minutes after the injury. RESULTS: A significant (corrected P < 0.05) increase in average T1 from the preinjury (895.24 msec) to the first postinjury timepoint (T1 = 951.37 msec) was followed by a significant (corrected P < 0.05) decrease (return) up to the last postinjury timepoint (T1 = 913.16 msec) in the voxels of the cortex and hippocampus. No significant (corrected P < 0.05) change in T1 was found in the sham-injured group. CONCLUSION: The spatial and temporal linkages between the MRI T1 changes and the histological findings suggest that neuronal compaction and recovery is associated with T1 alterations. MRI therefore offers the possibility of in vivo investigations of neuronal compaction and recovery. J. MAGN. RESON. IMAGING 2016;44:814-822.