Time Course Of Intensity Research Articles

Drought-Induced Xylem Sulfate Activates the ABA-Mediated Regulation of Sulfate Assimilation and Glutathione Redox in Brassica napus Leaves.

Drought intensity modifies the assimilatory pathway of glutathione (GSH) synthesis. Abscisic acid (ABA) is a representative signaling hormone involved in regulating plant stress responses. This study aimed to investigate an interactive regulation of sulfate and/or ABA in GSH metabolism and redox. The drought-responsive alterations in sulfate assimilation and GSH-based redox reactions were assessed relative to ABA responses on the time-course of drought intensity. Drought-responsive H2O2 concentrations were divided into two distinct phases-an initial 4 days of no change (Ψw ≥ -0.49 MPa) and a phase of higher accumulation during the late phase of the drought (days 10-14; Ψw ≤ -1.34 MPa). During the early phase of the drought, GSH/GSSG redox state turned to the slightly reduced state with a transient increase in GSH, resulting from a strong activation of H2O2 scavenging enzymes, ascorbate peroxidase (APOX) and glutathione reductase (GR). The late phase of the drought was characterized by a decrease in GSH due to cysteine accumulation, shifting GSH- and NADPH-based redox states to higher oxidization, increasing sulfate and ABA in xylem, and causing ABA accumulation in leaves. Regression analysis revealed that sulfate in xylem sap was positively correlated with H2O2 concentrations and ABA was closely related to decreases in the GSH pool and the oxidation of GSH catalyzed by glutathione peroxidase (GPOX). These results indicate that drought-induced oxidation proceeds through the suppression of GSH synthesis and further GSH oxidation in a sulfate-activated ABA-dependent manner.

Tissue response curve-shape analysis of dynamic glucose-enhanced and dynamic contrast-enhanced magnetic resonance imaging in patients with brain tumor.

Dynamic glucose-enhanced (DGE) MRI is used to study the signal intensity time course (tissue response curve) after D-glucose injection. D-glucose has potential as a biodegradable alternative or complement to gadolinium-based contrast agents, with DGE being comparable with dynamic contrast-enhanced (DCE) MRI. However, the tissue uptake kinetics as well as the detection methods of DGE differ from DCE MRI, and it is relevant to compare these techniques in terms of spatiotemporal enhancement patterns. This study aims to develop a DGE analysis method based on tissue response curve shapes, and to investigate whether DGE MRI provides similar or complementary information to DCE MRI. Eleven patients with suspected gliomas were studied. Tissue response curves were measured for DGE and DCE MRI at 7 T and the area under the curve (AUC) was assessed. Seven types of response curve shapes were postulated and subsequently identified by deep learning to create color-coded "curve maps" showing the spatial distribution of different curve types. DGE AUC values were significantly higher in lesions than in normal tissue (p < 0.007). Furthermore, the distribution of curve types differed between lesions and normal tissue for both DGE and DCE. The DGE and DCE response curves in a 6-min postinjection time interval were classified as the same curve type in 20% of the lesion voxels, which increased to 29% when a 12-min DGE time interval was considered. While both DGE and DCE tissue response curve-shape analysis enabled differentiation of lesions from normal brain tissue in humans, their enhancements were neither temporally identical nor confined entirely to the same regions. Curve maps can provide accessible and intuitive information about the shape of DGE response curves, which is expected to be useful in the continued work towards the interpretation of DGE uptake curves in terms of D-glucose delivery, transport, and metabolism.

Antipruritic Effect of Topical Acetaminophen Gel in Histaminergic and Non-histaminergic Itch Provocation: A Double-blind, Vehicle-controlled Pilot Study.

There is a need for new topical antipruritics that are effective on many types of itch. This study examined the antipruritic efficacy of a new formulation of topical acetaminophen. In vitro skin permeability studies showed that 2.5% and 5% formulations are able to rapidly deliver an adequate amount of the drug into the skin. In a double-blind, vehicle-controlled, randomized study in 17 healthy volunteers, 1%, 2.5% and 5% acetaminophen gels and a vehicle gel were applied to the skin prior to histaminergic and non-histaminergic itch induction and assessment of thermal pain thresholds. The 2.5% and 5% gel formulations significantly reduced the itch intensity time course and the area under the curve for both histamine and cowhage itch. No effect was noted on heat pain thresholds and no adverse effects were observed. These results suggest that topical acetaminophen would be a safe and effective over-the-counter medication for itch.

Healthy Kidney Segmentation in the Dce-Mr Images Using a Convolutional Neural Network and Temporal Signal Characteristics.

Quantification of renal perfusion based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) requires determination of signal intensity time courses in the region of renal parenchyma. Thus, selection of voxels representing the kidney must be accomplished with special care and constitutes one of the major technical limitations which hampers wider usage of this technique as a standard clinical routine. Manual segmentation of renal compartments—even if performed by experts—is a common source of decreased repeatability and reproducibility. In this paper, we present a processing framework for the automatic kidney segmentation in DCE-MR images. The framework consists of two stages. Firstly, kidney masks are generated using a convolutional neural network. Then, mask voxels are classified to one of three regions—cortex, medulla, and pelvis–based on DCE-MRI signal intensity time courses. The proposed approach was evaluated on a cohort of 10 healthy volunteers who underwent the DCE-MRI examination. MRI scanning was repeated on two time events within a 10-day interval. For semantic segmentation task we employed a classic U-Net architecture, whereas experiments on voxel classification were performed using three alternative algorithms—support vector machines, logistic regression and extreme gradient boosting trees, among which SVM produced the most accurate results. Both segmentation and classification steps were accomplished by a series of models, each trained separately for a given subject using the data from other participants only. The mean achieved accuracy of the whole kidney segmentation was 94% in terms of IoU coefficient. Cortex, medulla and pelvis were segmented with IoU ranging from 90 to 93% depending on the tissue and body side. The results were also validated by comparing image-derived perfusion parameters with ground truth measurements of glomerular filtration rate (GFR). The repeatability of GFR calculation, as assessed by the coefficient of variation was determined at the level of 14.5 and 17.5% for the left and right kidney, respectively and it improved relative to manual segmentation. Reproduciblity, in turn, was evaluated by measuring agreement between image-derived and iohexol-based GFR values. The estimated absolute mean differences were equal to 9.4 and 12.9 mL/min/1.73 m2 for scanning sessions 1 and 2 and the proposed automated segmentation method. The result for session 2 was comparable with manual segmentation, whereas for session 1 reproducibility in the automatic pipeline was weaker.

Characterization of salicylic acid- and abscisic acid-mediated photosynthesis, Ca2+ and H2O2 accumulation in two distinct phases of drought stress intensity in Brassica napus

Drought modifies the endogenous hormonal status, which is involved in the regulation of stress responses and tolerance. This study aimed to characterize the drought-responsive hormone-mediated regulation of stress responses based on the time-course of drought intensity. Alterations in H2O2, Ca2+ and their signaling genes with decreasing leaf water potential (Ψw) were interpreted as being linked to the endogenous hormonal level. Drought responses in relation to SA and ABA balance represented two distinct phases. The early phase, during the first 6 days when the Ψw was greater than -0.78 MPa, was characterized by a rapid decrease in photosynthetic activity with a progressive accumulation of H2O2 and Ca2+ in the strong correlation with the increases in both SA and ABA level. The late phase, days 6–14, was distinguished by ABA-mediated stress symptomatic responses (e.g., the maintenance of the depressed photosynthesis with severe leaf wilting) with highly enhanced expression of ABA-related genes (NCED3 and MYC2) and concomitant depression in the SA level and SA-related genes (ICS1 and NPR1). The regression analysis revealed that both SA and ABA levels as being positively correlated with Ca2+ and H2O2 were closely related to the depression of photosynthesis for the early phase (days 0–6), whereas the correlations were significant only with ABA for the whole period of drought (days 0–14). These results indicate that SA-stimulated H2O2 accumulation and SA responses during the early drought phase are part of upstream H2O2-stimulated ABA accumulation, which causes ABA signaling and responses, leading to severe drought symptoms during the late phase.

Fluorescence Lifetime and Intensity of Thioflavin T as Reporters of Different Fibrillation Stages: Insights Obtained from Fluorescence Up-Conversion and Particle Size Distribution Measurements.

Thioflavin T (ThT) assay is extensively used for studying fibrillation kinetics in vitro. However, the differences in the time course of ThT fluorescence intensity and lifetime and other physical parameters of the system, such as particle size distribution, raise questions about the correct interpretation of the aggregation kinetics. In this work, we focused on the investigation of the mechanisms, which underlay the difference in sensitivity of ThT fluorescence intensity and lifetime to the formation of protein aggregates during fibrillation by the example of insulin and during binding to globular proteins. The assessment of aggregate sizes and heterogeneity was performed using dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). Using the sub-nanosecond resolution measurements, it was shown that the ThT lifetime is sensitive to the appearance of as much as a few percent of ThT bound to the high-affinity sites that occur simultaneously with an abrupt increase of the average particle size, particles concentration, and size heterogeneity. The discrepancy between ThT fluorescence intensity and a lifetime can be explained as the consequence of a ThT molecule fraction with ultrafast decay and weak fluorescence. These ThT molecules can only be detected using time-resolved fluorescence measurements in the sub-picosecond time domain. The presence of a bound ThT subpopulation with similar photophysical properties was also demonstrated for globular proteins that were attributed to non-specifically bound ThT molecules with a non-rigid microenvironment.

Dynamic contrast-enhanced MRI in oncology: how we do it.

Magnetic resonance imaging (MRI) is particularly attractive for clinical application in perfusion imaging thanks to the absence of ionizing radiation and limited volumes of contrast agent (CA) necessary. Dynamic contrast-enhanced MRI (DCE-MRI) involves sequentially acquiring T1-weighted images through an organ of interest during the passage of a bolus administration of CA. It is a particularly flexible approach to perfusion imaging as the signal intensity time course allows not only rapid qualitative assessment, but also quantitative measures of intrinsic perfusion and permeability parameters. We examine aspects of the T1-weighted image series acquisition, CA administration, post-processing that constitute a DCE-MRI study in clinical practice, before considering some heuristics that may aid in interpreting the resulting contrast enhancement time series. While qualitative DCE-MRI has a well-established role in the diagnostic assessment of a range of tumours, and a central role in MR mammography, clinical use of quantitative DCE-MRI remains limited outside of clinical trials. The recent publication of proposals for standardized acquisition and analysis protocols for DCE-MRI by the Quantitative Imaging Biomarker Alliance may be an opportunity to consolidate and advance clinical practice.

Assessment of odor perception related to stimulation modes in a mock MRI scanner

BackgroundNumerous studies investigated the central-nervous processing of olfactory information in humans, often based on functional MRI studies. However, when describing the olfactory perception, the course of olfactory sensations over time has received little attention although this constitutes a fundamental portion of the experimental paradigm. Hence, the aim of this study was to evaluate overall perception and the perception of odors over the time course of repeated odorous stimulation under different conditions of stimulus presentation. New methodTwenty-eight subjects with a normal sense of smell were asked to lie in a mock MRI scanner during the experiment. Three conditions of odor presentations were Tubing, (odors presented intranasally with separate tubing for each nostril), mask (odors presented to a mask covering the subject's nose) and vacuum (odors presented into the bore of the sham scanner). A pleasant odor (peach) and an unpleasant (fish) odor were presented using a computer-controlled olfactometer. Participants were asked to evaluate intensity and pleasantness of the odors. They also rated the comfortability of each presentation mode. For the vacuum and mask conditions, subjects were tracked with the time course of the odor intensity. ResultsFor all sessions, intensity was influenced by conditions (F = 29.6, p < 0.001, ηp² = 0.8, mask > tube > vacuum) and odors (F = 11.8, p = 0.003, ηp² = 0.4, fish > peach). Pleasantness was influenced by odors (F = 26.2, p = 0.001, ηp² = 0.593, peach > fish), comfortability was significantly influenced by conditions (F = 9.3, p = 0.002, ηp² = 0.5, vacuum > mask > tube). For peach odor, pleasantness was positively correlated with intensity (r = 0.3, p = 0.03) and negatively with fish odor intensity (r = −0.4, p < 0.001). Overall, the onset latency of intensity ratings (mean = 3.5 s, SD = 2.6) was significantly longer than the offset latency (mean = 1.6 s, SD = 0.8) (t = 3.5, p = 0.001). For the amplitude, conditions had a significant effect (F = 4.5, p = 0.04, ηp² = 0.2, mask > vacuum). ConclusionsPerceived odor intensity was affected by the odor presentation being strongest in the mask condition, whereas this was not different for odor pleasantness. The vacuum condition was rated as most comfortable. Within the present design, the latency of onset and offset does not seem to be influenced by conditions, odors and blocks. Models of fMRI analyses should be adjusted to account for this shift in odor intensity perception.

Study of molecular transport through a single nanopore in the membrane of a giant unilamellar vesicle using COMSOL simulation.

The antimicrobial peptide (AMP) magainin 2 induces nanopores in the lipid membranes of giant unilamellar vesicles (GUVs), as observed by the leakage of water-soluble fluorescent probes from the inside to the outside of GUVs through the pores. However, molecular transport through a single nanopore has not been investigated in detail yet and is studied in the present work by simulation. A single pore was designed in the membrane of a GUV using computer-aided design software. Molecular transport, from the outside to the inside of GUV through the nanopore, of various fluorescent probes such as calcein, Texas-Red Dextran 3000 (TRD-3k), TRD-10k and TRD-40k was then simulated. The effect of variation in GUV size (diameter) was also investigated. A single exponential growth function was fitted to the time course of the fluorescence intensity inside the GUV and the corresponding rate constant of molecular transport was calculated, which decreases with an increase in the size of fluorescent probe and also with an increase in the size of GUV. The rate constant found by simulation agrees reasonably well with reported experimental results for inside-to-outside probe leakage. Based on Fick's law of diffusion an analytical treatment is developed for the rate constant of molecular transport that supports the simulation results. These investigations contribute to a better understanding of the mechanism of pore formation using various membrane-active agents in the lipid membranes of vesicles and the biomembranes of cells.

Relation between Release of Catecholamines and FFN511 Studied with Electrochemical Detector Arrays

Exocytosis is an essential vesicle fusion process that mediates transmitter release. For high resolution spatiotemporal analysis of single vesicle fusion events, a combinatorial approach of amperometry and fluorescence imaging was employed. Amperometric spikes from physically stimulated bovine chromaffin cells loaded with the Fluorescent False Neurotransmitter FFN511were detected by microfabricated four-electrode electrochemical detector (ECD) arrays. To determine the location of a fusion event leading to amperometric spikes with different quantal size in the different ECD array electrodes, random walk simulations were performed using the actual ECD array geometry. The location of a measured release event was fitted to match the simulated data. To account for drift of the ECD array, the pixel shift of each frame was fitted relative to the image that was used to generate the simulation map. The transparent glass surface in the center of the ECDs allowed the concurrent fluorescence imaging of localized loss of FFN511from secretory vesicles in TIRF microscopy mode. The frequency of amperometric spikes was much higher than that of FFN511 release events. Only the amperometric spikes that were correlated in time and location with a loss of fluorescence event were considered for analysis. The intensity time course of a 3x3 pixel area (480 x 480 nm2) around the fusion site of the fluorescence movie was determined and different fusion events were aligned at the onset of their respective amperometric spikes. Time super-resolution analysis using the recently developed Event Correlated Microscopy (ECOM) method revealed that FFN511 release followed the amperometric spike onset with a mean delay of ∼115 ms, presumably reflecting slow diffusion of FFN while in amperometric detection catecholamine molecules are rapidly consumed during the oxidation process. Supported by NIH grant R01GM121787.

Estimation of Tropical Cyclone Intensity from the Satellite Infrared Images of Its Spiral Cloud Bands

The spiral signatures of infrared satellite images of the tropical cyclone Phanfone observed in the Northwest Pacific in August 2002 are analyzed using the hyperbolic-logarithmic model of a streamline in the Rankine vortex. Maximum wind speed Vmax and some other physical characteristics of the cyclone are estimated by identifying hyperbolic-logarithmic spirals (RLS) which “fit” into the geometric boundaries of the signatures. The comparison of temporal variations in Vmax with the data of meteorological services of the USA (JTWC) and Japan (RSMC) revealed satisfactory agreement of the time course of tropical cyclone intensity from the HLS estimates and JTWC data. The absolute estimates of intensity were within an interval between the corresponding JTWC and RSMC data. It seems that if the presented approach is enhanced, the HLS estimation may be a useful contribution to the empirical methods of tropical cyclone intensity determination by remote sensing means.

Differentiation of High-grade Gliomas from Brain Metastases Using Tissue Similarity Maps (TSMs) Based Relative Cerebral Blood Volume Values

Background: Perfusion Weighted Imaging (PWI) has been used to differentiate the solitary metastases from high-grade glioma. However, the CBV value obtained from classical algorithm can be affected by a number of factors. Tissue Similarity Map (TSM) is a new algorithm depending solely on the signal intensity time course but does not require the use of Concentration Time Curve (CTC), which is different from the classical rCBV algorithm. Objective: The purpose of this study is to investigate the diagnostic utility of TSM based rCBV values in differentiating between high-grade gliomas and solitary metastases. Methods: The preoperative MR PWI studies of 30 patients with a solitary cerebral neoplasm were retrospectively analyzed. All PWI data were calculated for TSM algorithm with MATLAB 7.6 (Math Works, Natick, MA). The TSM based rCBV (rCBVTSM) were measured in the parenchyma of tumor and peritumoral regions. All specimens were histopathologically categorized as high-grade gliomas or metastases and were correlated with corresponding rCBVTSM values. Results: All PWI data could be post-processed by using the TSM post-processing software. The differences in the rCBVTSM-T between high-grade gliomas and metastases were not statistically significant (p=0.299). While the rCBVTSM-P of high-grade gliomas was higher than that of metastases (p=0.040). ROC curve analysis showed significant AUC of rCBVTSM-P for differentiating highgrade gliomas from metastases (p=0.020). The rCBVTSM-P threshold of 1.725 was found to be a significant cutoff value for high-grade glioma/metastases prediction with 0.619 sensitivity and 0.889 specificity. Conclusion: The rCBVTSM-P derived from MR PWI may be helpful in differentiating high-grade gliomas from solitary metastases. Keywords: TSM, perfusion imaging, cerebral blood volume, glioma, neoplasms metastasis, differentiation diagnosis.

(Invited) Detection of Bacterial Fluorescence by the Combination of MEMS Microfluidic Chip and Si Photodetector toward On-Chip Biological Sensing

This work describes the recent researches on bacterial sensing using microelectromechanical systems (MEMS) technology. The fluorescent characteristics of the targeting bacteria, Legionella cells trapped in a bio-MEMS microfluidic chip were studied, showing they emit blue fluorescence when they are forced to stop their motion. The ultraviolet (UV) photoirradiation time dependencies of the fluorescent spectra were compared between Legionella pneumophila (L. pneumophila) and Legionella dumoffii (L. dumoffii). The photocurrent of the fluorescence from L. dumoffii confined in the bio-MEMS microfluidic chip was able to be measured by the Si photodetector with a photogate. These results indicate that the combination of the Si photodetector with bio-MEMS microfluidic chip enables to make bacterial sensors for Legionella on a chip. We are developing a portable small sensor that can detect pathogenic bacteria, Legionella without their cultivation. During the course of the study, we found that the cells emit fluorescence by the ultraviolet (UV) light irradiation just when they are restricted in their motion in microscopic spaces [1]. To confine Legionella cells in such small spaces, we used a glass microbeads suspension and a PDMS-made MEMS microfluidic chip [2]. The fluorescence was observed for L. pneumophila and L. dumoffii confined in the MEMS microfluidic chip using a fluorescence microscope [3]. The fluorescent spectra obtained for both bacteria varied with the UV-photoirradiation time. The spectra of L. pneumophila with beads showed a main and a shoulder peaks at around 450 nm and 520 nm respectively in the initial stages of the UV-photoirradiation with a wavelength of 365 nm. Then the main peak grew with the irradiation time, showing the UV light triggers to produce fluorescent materials. The spectra obtained from L. dumoffii also varied drastically depending on the UV-photoirradiation time. In the initial stages of the photoirradiation, the spectra with multiple peaks appeared and fell off. Subsequently, the spectra with a broad peak gradually grew. This shows that the fluorescent materials which L. dumoffii originally has in their cells as reported in Ref. 4, are photodissociated. After the initial fluorescent materials disappear, the production of the different fluorescent materials begins to occur. Thus, the bacteria might show their own fluorescent characteristics in the motion-restricted situation such as in microfluidic chips. The fluorescent spectral characteristics of Legionella shown above were acquired by the combination of a bulky fluorescence microscope and a spectrometer. However, the integration with the optical sensor on a chip is necessary for easy portable use or in-field use. The successful detection of fluorescence from L. dumoffii is finally described using the microfluidic chip and a fluorescence sensor of Si photodetector with a poly-Si photogate [5]. In the fluorescence detection, the transparent PDMS-made microfluidic chip was set above the detector without any optical filters because the poly-Si photogate prevents the excitation light from entering the sensor by absorbing UV light. This helps the bacterial sensor to be made small. The photocurrent generated by the fluorescence from L. dumoffii cells confined with the beads in the microfluidic chip was able to be observed just after the UV photoirradiation with a wavelength of 365 nm. The time course of the photocurrent intensity was similar to that of fluorescent spectral intensity obtained by the fluorescence microscope mentioned earlier. This indicates the combination of the PDMS-made MEMS microfluidic chip and the Si photodetector enables to make an integrated on-chip bacterial sensor.

Objectively measured physical activity and 12-month trajectories of neck–shoulder pain in workers: A prospective study in DPHACTO

This study aimed to investigate the association between objectively measured physical activity at work and leisure and the intensity (mean level and time course) of neck-shoulder pain (NSP) over 12 months among male and female blue collar workers. Data were obtained from 625 blue collar workers from the Danish cohort DPHACTO. Physical activity was measured objectively at baseline using accelerometers. The percentage of time spent in physical activity (walking, climbing stairs, running and cycling) was calculated for both work and leisure time. Longitudinal data on the intensity of NSP (numerical rating scale 0-10) were collected using text messages every fourth week over 12 months. Linear mixed models were used to investigate the associations between occupational physical activity (OPA) and leisure time physical activity (LTPA) and the trajectories of the intensity of NSP, adjusted for individual, biomechanical and psychosocial factors, and baseline pain. OPA was not associated with the mean intensity of NSP over 12 months. LTPA was negatively associated with the mean intensity of NSP both among men ( B=-0.71, 95% CI -1.31 to -0.11) and women ( B=-0.85, 95% CI -1.57 to -0.13). Sex interactions on the 12-month trajectories of NSP showed that higher physical activity was associated with a slower reduction in NSP among men for OPA only ( B=0.03, 95% CI 0.01-0.05) and women for LTPA only ( B=0.05, 95% CI 0.00-0.09). We found that more time in LTPA was associated with a lower overall intensity of NSP over 12 months among blue collar workers. However, depending on sex and domain, high physical activity had an unfavourable effect on the course of NSP over 12 months.

High-sensitivity TMS/fMRI of the Human Motor Cortex Using a Dedicated Multichannel MR Coil

PurposeTo validate a novel setup for concurrent TMS/fMRI in the human motor cortex based on a dedicated, ultra-thin, multichannel receive MR coil positioned between scalp and TMS system providing greatly enhanced sensitivity compared to the standard birdcage coil setting. MethodsA combined TMS/fMRI design was applied over the primary motor cortex based on 1Hz stimulation with stimulation levels of 80%, 90%, 100%, and 110% of the individual active motor threshold, respectively. Due to the use of a multichannel receive coil we were able to use multiband-accelerated (MB=2) EPI sequences for the acquisition of functional images. Data were analysed with SPM12 and BOLD-weighted signal intensity time courses were extracted in each subject from two local maxima (individual functional finger tapping localiser, fixed MNI coordinate of the hand knob) next to the hand area of the primary motor cortex (M1) and from the global maximum. ResultsWe report excellent image quality without noticeable signal dropouts or image distortions. Parameter estimates in the three peak voxels showed monotonically ascending activation levels over increasing stimulation intensities. Across all subjects, mean BOLD signal changes for 80%, 90%, 100%, 110% of the individual active motor threshold were 0.43%, 0.63%, 1.01%, 2.01% next to the individual functional finger tapping maximum, 0.73%, 0.91%, 1.34%, 2.21% next to the MNI-defined hand knob and 0.88%, 1.09%, 1.65%, 2.77% for the global maximum, respectively. ConclusionOur results show that the new setup for concurrent TMS/fMRI experiments using a dedicated MR coil array allows for high-sensitivity fMRI particularly at the site of stimulation. Contrary to the standard birdcage approach, the results also demonstrate that the new coil can be successfully used for multiband-accelerated EPI acquisition. The gain in flexibility due to the new coil can be easily combined with neuronavigation within the MR scanner to allow for accurate targeting in TMS/fMRI experiments.

Diagnosis of Spinal Lesions Using Heuristic and Pharmacokinetic Parameters Measured by Dynamic Contrast-Enhanced MRI

This study aimed to evaluate the diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in differentiation of four spinal lesions by using heuristic and pharmacokinetic parameters analyzed from DCE signal intensity time course. DCE-MRI of 62 subjects with confirmed myeloma (n = 9), metastatic cancer (n = 22), lymphoma (n = 7), and inflammatory tuberculosis (TB) (n = 24) in the spine were analyzed retrospectively. The region of interest was placed on strongly enhanced tissues. The DCE time course was categorized as the "wash-out," "plateau," or "persistent enhancement" pattern. The maximum enhancement, steepest wash-in enhancement, and wash-out slope using the signal intensity at 67 seconds after contrast injection as reference were measured. The Tofts 2-compartmental pharmacokinetic model was applied to obtain Ktrans and kep. Pearson correlation between heuristic and pharmacokinetic parameters was evaluated, and receiver operating characteristic curve analysis was performed for pairwise group differentiation. The mean wash-out slope was -22% ± 10% for myeloma, 1% ± 0.4% for metastatic cancer, 3% ± 3% for lymphoma, and 7% ± 10% for TB, and it could significantly distinguish myeloma from metastasis (area under the curve [AUC] = 0.884), lymphoma (AUC = 1.0), and TB (AUC = 1.0) with P = .001, and distinguish metastasis from TB (AUC = 0.741) with P = .005. The kep and wash-out slope were highly correlated (r = 0.92), and they showed a similar diagnostic performance. The Ktrans was significantly correlated with the maximum enhancement (r = 0.71) and the steepest wash-in enhancement (r = 0.85), but they had inferior diagnostic performance compared to the wash-out slope. DCE-MRI may provide additional diagnostic information, and a simple wash-out slope had the best diagnostic performance. The heuristic and pharmacokinetic parameters were highly correlated.

Characterisation of Lesions after Stereotactic Radiosurgery for Brain Metastases: Impact of Delayed Contrast Magnetic Resonance Imaging

AimsTo investigate if brain metastases and radiation injuries after stereotactic radiosurgery (SRS) have different signal intensity (SI) time courses up to 55 min after contrast agent application and if delayed contrast magnetic resonance imaging (MRI) contributes to improve diagnostic accuracy. Materials and methodsThirty-four consecutive patients treated with SRS for cerebral metastases were prospectively enrolled in the study. T1-weighted images were acquired on a 3-Tesla MR unit at three time points, at 2 (TP1), 15 (TP2) and 55 (TP3) min after administering contrast agent. A simultaneous, matched-pairs approach was used for region of interest analysis of the entire contrast-enhancing lesion (SI-e), the centre (SI-c), the border of the lesion (SI-b) and the adjacent non-contrast-enhancing tissue (SI-p). SIs of brain metastases and radiation injuries after SRS were compared using a two-level, linear, mixed-effects regression model. ResultsIn total, 41 lesions were analysed: 16 metastases and 25 radiation injuries. The SI time course of SI-e, SI-c and SI-b proved to be significantly different for both entities (P < 0.001) from TP2 to TP3. The SI of 39/41 lesions increased from TP1 to TP2 for the three parameters. Radiation injuries showed a further signal increase at least for SI-c from TP2 to TP3, whereas for all the three parameters SI decreased in all metastases. ConclusionBrain metastases and radiation injuries after SRS have a characteristic and statistically significantly different SI time course on sequential gadolinium enhancement MRI when late MR studies are included.

Technical Pitfalls of Signal Truncation in Perfusion MRI of Glioblastoma.

Dynamic susceptibility contrast (DSC) perfusion-weighted imaging (PWI) is widely used in clinical settings for the radiological diagnosis of brain tumor. The signal change in brain tissue in gradient echo-based DSC PWI is much higher than in spin echo-based DSC PWI. Due to its exquisite sensitivity, gradient echo-based sequence is the preferred method for imaging of all tumors except those near the base of the skull. However, high sensitivity also comes with a dynamic range problem. It is not unusual for blood volume to increase in gene-mediated cytotoxic immunotherapy-treated glioblastoma patients. The increase of fractional blood volume sometimes saturates the MRI signal during first-pass contrast bolus arrival and presents signal truncation artifacts of various degrees in the tumor when a significant amount of blood exists in the image pixels. It presents a hidden challenge in PWI, as this signal floor can be either close to noise level or just above and can go no lower. This signal truncation in the signal intensity time course is a significant issue that deserves attention in DSC PWI. In this paper, we demonstrate that relative cerebral blood volume and relative cerebral blood flow (rCBF) are underestimated due to signal truncation in DSC perfusion, in glioblastoma patients. We propose the use of second-pass tissue residue function in rCBF calculation using least-absolute-deviation deconvolution to avoid the underestimation problem.

Surgical tissue handling methods to optimize ex vivo fluorescence with the activatable optical probe γ-glutamyl hydroxymethyl rhodamine green.

Optical fluorescence imaging has been developed as an aid to intraoperative diagnosis to improve surgical and endoscopic procedures. Compared with other intraoperative imaging methods, it is lower in cost, has a high safety margin, is portable and easy to use. γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) is a recently developed activatable fluorescence probe that emits strong fluorescence in the presence of the enzyme γ-glutamyl transpeptidase (GGT), which is overexpressed in many cancers, including ovarian cancer. Ex vivo testing is important for clinical approval of such probes. The diagnostic performance of gGlu-HMRG in fresh excised surgical specimens has been reported; however, details of tissue handling have not been optimized. In this study, we investigated four different tissue handling procedures to optimize imaging in excised tumor specimens. The fluorescence intensity time courses after the different tissue handling methods were compared. Additionally, the fluorescence positive areas were correlated with the presence of red fluorescent protein (RFP) in an RFP positive cell line as the standard of reference for cancer location. In the 'intact' groups, tumors yielded quick and homogeneous activation of gGlu-HMRG. In the 'rinse' and 'cut' groups, the fluorescence intensity of the tumor was a little lower than that in the intact group. In the 'pressed' groups, however, fluorescence intensity from gGlu-HMRG was lower over the entire time course, suggesting a decrease or relocation of excreted GGT. In conclusion, we demonstrate that the method of tissue handling prior to ex vivo imaging with the activatable probe gGlu-HMRG has a strong influence on the signal derived from the specimen. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

T1-weighted Dynamic Contrast-enhanced MR Imaging of the Lung in Asthma: Semiquantitative Analysis for the Assessment of Contrast Agent Kinetic Characteristics

To evaluate the contrast agent kinetics of dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging in healthy lungs and asthmatic lungs by using non-model-based semiquantitative parameters and to explore the relationships with pulmonary function testing and eosinophil level. The study was approved by the National Research Ethical Committee (reference no. 11/NW/0387), and written informed consent was obtained from all individuals. Ten healthy subjects and 30 patients with asthma underwent pulmonary function tests, blood and sputum eosinophil counts, and 1.5-T DCE MR imaging within 7 days. Semiquantitative parameters of contrast agent kinetics were calculated from the relative signal intensity-time course curves on a pixel-by-pixel basis and were summarized by using whole-lung median values. The distribution heterogeneity was assessed by using the regional coefficient of variation. DCE MR imaging readouts were compared between groups by using one-way analysis of variance, and the relationships with pulmonary function testing and eosinophil counts were assessed by using Pearson correlation analysis. Asthmatic patients showed significantly lower peak enhancement (P < .001) and initial areas under the relative signal intensity curve in the first 60 seconds (P = .002) and significantly reduced late-phase washout slope (P = .002) when compared with healthy control subjects. The distribution heterogeneity of bolus arrival time (P = .029), time to peak (P = .008), upslope of the first-pass peak (P = .011), and late-phase washout slope (P = .032), estimated by using the median coefficient of variation, were significantly higher in asthmatic patients than in healthy control subjects. These imaging readouts also showed significant linear correlations with measurements of pulmonary function testing but not with eosinophil level in patients with asthma. The contrast agent kinetic characteristics of T1-weighted DCE MR images of asthmatic lungs are different from those of healthy lungs and are related to measurements of pulmonary function testing but not to eosinophil level.