Relative Signal Increase Research Articles

Improved Segmentation and Detection Sensitivity of Diffusion-weighted Stroke Lesions with Synthetically Enhanced Deep Learning.

To compare the segmentation and detection performance of a deep learning model trained on a database of human-labeled clinical stroke lesions on diffusion-weighted (DW) images to a model trained on the same database enhanced with synthetic stroke lesions. In this institutional review board-approved study, a stroke database of 962 cases (mean patient age ± standard deviation, 65 years ± 17; 255 male patients; 449 scans with DW positive stroke lesions) and a normal database of 2027 patients (mean age, 38 years ± 24; 1088 female patients) were used. Brain volumes with synthetic stroke lesions on DW images were produced by warping the relative signal increase of real strokes to normal brain volumes. A generic three-dimensional (3D) U-Net was trained on four different databases to generate four different models: (a) 375 neuroradiologist-labeled clinical DW positive stroke cases (CDB); (b) 2000 synthetic cases (S2DB); (c) CDB plus 2000 synthetic cases (CS2DB); and (d) CDB plus 40 000 synthetic cases (CS40DB). The models were tested on 20% (n = 192) of the cases of the stroke database, which were excluded from the training set. Segmentation accuracy was characterized using Dice score and lesion volume of the stroke segmentation, and statistical significance was tested using a paired two-tailed Student t test. Detection sensitivity and specificity were compared with labeling done by three neuroradiologists. The performance of the 3D U-Net model trained on the CS40DB (mean Dice score, 0.72) was better than models trained on the CS2DB (Dice score, 0.70; P < .001) or the CDB (Dice score, 0.65; P < .001). The deep learning model (CS40DB) was also more sensitive (91% [95% confidence interval {CI}: 89%, 93%]) than each of the three human readers (human reader 3, 84% [95% CI: 81%, 87%]; human reader 1, 78% [95% CI: 75%, 81%]; human reader 2, 79% [95% CI: 76%, 82%]), but was less specific (75% [95% CI: 72%, 78%]) than each of the three human readers (human reader 3, 96% [95% CI: 94%, 98%]; human reader 1, 92% [95% CI: 90%, 94%]; human reader 2, 89% [95% CI: 86%, 91%]). Deep learning training for segmentation and detection of stroke lesions on DW images was significantly improved by enhancing the training set with synthetic lesions.Supplemental material is available for this article.© RSNA, 2020.

Ex vivo MR microscopy of a human brain with multiple sclerosis: Visualizing individual cells in tissue using intrinsic iron

PurposeTo perform magnetic resonance microscopy (MRM) on human cortex and a cortical lesion as well as the adjacent normal appearing white matter. To shed light on the origins of MRI contrast by comparison with histochemical and immunostaining. Methods3D MRM at a nominal isotropic resolution of 15 and 18 µm was performed on 2 blocks of tissue from the brain of a 77-year-old man who had MS for 47 years. One block contained normal appearing cortical gray matter (CN block) and adjacent normal appearing white matter (NAWM), and the other also included a cortical lesion (CL block). Postmortem ex-vivo MRI was performed at 11.7T using a custom solenoid coil and T2*-weighted 3D GRE sequence. Histochemical and immunostaining were done after paraffin embedding for iron, myelin, oligodendrocytes, neurons, blood vessels, macrophages and microglia, and astrocytes. ResultsMRM could identify individual iron-laden oligodendrocytes with high sensitivity (70% decrease in signal compared to surrounding) in CN and CL blocks, as well as some iron-laden activated macrophages and microglia. Iron-deficient oligodendrocytes seemed to cause relative increase in MRI signal within the cortical lesion. High concentration of myelin in the white matter was primarily responsible for its hypointense appearance relative to the cortex, however, signal variations within NAWM could be attributed to changes in density of iron-laden oligodendrocytes. ConclusionChanges in iron accumulation within cells gave rise to imaging contrast seen between cortical lesions and normal cortex, as well as the patchy signal in NAWM. Densely packed myelin and collagen deposition also contributed to MRM signal changes. Even though we studied only one block each from normal appearing and cortical lesions, such studies can help better understand the origins of histopathological and microstructural correlates of MRI signal changes in multiple sclerosis and contextualize the interpretation of lower-resolution in vivo MRI scans.

Switching from linear to macrocyclic gadolinium-based contrast agents halts the relative T1 -Weighted signal increase in deep gray matter of children with brain tumors: A retrospective study.

Studies have shown signal intensity (SI) changes in the brains of children exposed to repeated doses of a gadolinium-based contrast agent (GBCA). The trajectory of changes in relative dentate nucleus (DN) and globus pallidus (GP) SI in children receiving multiple doses of GBCA will alter when switched from linear to macrocyclic agents. Retrospective longitudinal. Thirty-five children, age range 0.5-17.0 years, undergoing brain tumor follow-up between 2006 and 2017. Unenhanced T1 WI, serial scans at both 1.5T and 3T. Regions of interest were drawn on DN, GP, and SIs normalized to middle cerebellar peduncle (DN/MCP) and cerebral white matter (GP/CWM), respectively. A change in SI ratios as a function of dose (slope gradient) calculated according to the type of contrast agent received: linear only, macrocyclic only, or switchover from linear to macrocyclic. For the latter, gradients were compared before and after switchover. The effect of anticancer treatment on slope gradient was tested. One-sample t-test or Mann-Whitney U-test for slope gradients differing from zero. Independent samples t-tests to compare slope gradient groups. Paired sample t-tests to compare slope gradients before and after switchover. A significant (P < 0.05) increase in SI ratio was observed following multiple doses of linear but not macrocyclic agents: mean percentage increase per dose in SI was 0.063% vs. -0.034% for DN/MCP, and 0.078% vs. 0.004% for GP/CWM ratios. A significant (P < 0.05) change of SI trajectory in the DN/MCP ratio was demonstrated when switching from a linear to macrocyclic agent. There was no difference in SI trajectory between patients who had anticancer therapies and those who did not, DN/MCP P = 0.740; GP/BWM P = 0.694. Switching from linear to macrocyclic gadolinium-based contrast agents seems to halt the relative T1 signal increase in deep gray matter in children. Anticancer treatments appeared to have no impact on the trajectory of T1 SI. 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:288-295.

Motion-corrected whole-heart PET-MR for the simultaneous visualisation of coronary artery integrity and myocardial viability: an initial clinical validation

PurposeCardiac PET-MR has shown potential for the comprehensive assessment of coronary heart disease. However, image degradation due to physiological motion remains a challenge that could hinder the adoption of this technology in clinical practice. The purpose of this study was to validate a recently proposed respiratory motion-corrected PET-MR framework for the simultaneous visualisation of myocardial viability (18F-FDG PET) and coronary artery anatomy (coronary MR angiography, CMRA) in patients with chronic total occlusion (CTO).MethodsA cohort of 14 patients was scanned with the proposed PET-CMRA framework. PET and CMRA images were reconstructed with and without the proposed motion correction approach for comparison purposes. Metrics of image quality including visible vessel length and sharpness were obtained for CMRA for both the right and left anterior descending coronary arteries (RCA, LAD), and relative increase in 18F-FDG PET signal after motion correction for standard 17-segment polar maps was computed. Resulting coronary anatomy by CMRA and myocardial integrity by PET were visually compared against X-ray angiography and conventional Late Gadolinium Enhancement (LGE) MRI, respectively.ResultsMotion correction increased CMRA visible vessel length by 49.9% and 32.6% (RCA, LAD) and vessel sharpness by 12.3% and 18.9% (RCA, LAD) on average compared to uncorrected images. Coronary lumen delineation on motion-corrected CMRA images was in good agreement with X-ray angiography findings. For PET, motion correction resulted in an average 8% increase in 18F-FDG signal in the inferior and inferolateral segments of the myocardial wall. An improved delineation of myocardial viability defects and reduced noise in the 18F-FDG PET images was observed, improving correspondence to subendocardial LGE-MRI findings compared to uncorrected images.ConclusionThe feasibility of the PET-CMRA framework for simultaneous cardiac PET-MR imaging in a short and predictable scan time (~11 min) has been demonstrated in 14 patients with CTO. Motion correction increased visible length and sharpness of the coronary arteries by CMRA, and improved delineation of the myocardium by 18F-FDG PET, resulting in good agreement with X-ray angiography and LGE-MRI.

Quantitative T1‐mapping detects cloudy‐enhancing tumor compartments predicting outcome of patients with glioblastoma

Contrast enhancement of glioblastomas (GBM) is caused by the decrease in relaxation time, T1. Here, we demonstrate that the quantitative measurement of T1 (qT1) discovers a subtle enhancement in GBM patients that is invisible in standard MRI. We assessed the volume change of this “cloudy” enhancement during radio‐chemotherapy and its impact on patients’ progression‐free survival (PFS). We enrolled 18 GBM patients in this observational, prospective cohort study and measured 3T‐MRI pre‐ and post contrast agent with standard T1‐weighted (T1w) and with sequences to quantify T1 before radiation, and at 6‐week intervals during radio‐chemotherapy. We measured contrast enhancement by subtracting pre from post contrast contrast images, yielding relative signal increase ∆T1w and relative T1 shortening ∆qT1. On ∆qT1, we identified a solid and a cloudy‐enhancing compartment and evaluated the impact of their therapy‐related volume change upon PFS. In ∆qT1 maps cloudy‐enhancing compartments were found in all but two patients at baseline and in all patients during therapy. The qT1 decrease in the cloudy‐enhancing compartment post contrast was 21.64% versus 1.96% in the contralateral control tissue (P < 0.001). It was located at the margin of solid enhancement which was also seen on T1w. In contrast, the cloudy‐enhancing compartment was visually undetectable on ∆T1w. A volume decrease of more than 21.4% of the cloudy‐enhancing compartment at first follow‐up predicted longer PFS (P = 0.038). Cloudy‐enhancing compartment outside the solid contrast‐enhancing area of GBM is a new observation which is only visually detectable with qT1‐mapping and may represent tumor infiltration. Its early volume decrease predicts a longer PFS in GBM patients during standard radio‐chemotherapy.

Cluster analysis of dynamic contrast enhanced MRI reveals tumor subregions related to locoregional relapse for cervical cancer patients

Background: Solid tumors are known to be spatially heterogeneous. Detection of treatment-resistant tumor regions can improve clinical outcome, by enabling implementation of strategies targeting such regions. In this study, K-means clustering was used to group voxels in dynamic contrast enhanced magnetic resonance images (DCE-MRI) of cervical cancers. The aim was to identify clusters reflecting treatment resistance that could be used for targeted radiotherapy with a dose-painting approach.Material and methods: Eighty-one patients with locally advanced cervical cancer underwent DCE-MRI prior to chemoradiotherapy. The resulting image time series were fitted to two pharmacokinetic models, the Tofts model (yielding parameters Ktrans and νe) and the Brix model (ABrix, kep and kel). K-means clustering was used to group similar voxels based on either the pharmacokinetic parameter maps or the relative signal increase (RSI) time series. The associations between voxel clusters and treatment outcome (measured as locoregional control) were evaluated using the volume fraction or the spatial distribution of each cluster.Results: One voxel cluster based on the RSI time series was significantly related to locoregional control (adjusted p-value 0.048). This cluster consisted of low-enhancing voxels. We found that tumors with poor prognosis had this RSI-based cluster gathered into few patches, making this cluster a potential candidate for targeted radiotherapy. None of the voxels clusters based on Tofts or Brix parameter maps were significantly related to treatment outcome.Conclusion: We identified one group of tumor voxels significantly associated with locoregional relapse that could potentially be used for dose painting. This tumor voxel cluster was identified using the raw MRI time series rather than the pharmacokinetic maps.

Whole-Body Diffusion-Weighted Imaging in Chronic Recurrent Multifocal Osteomyelitis in Children.

ObjectiveChronic recurrent multifocal osteomyelitis/ chronic non-bacterial osteomyelitis (CRMO/ CNO) is a rare auto-inflammatory disease and typically manifests in terms of musculoskeletal pain. Because of a high frequency of musculoskeletal disorders in children/ adolescents, it can be quite challenging to distinguish CRMO/ CNO from nonspecific musculosketetal pain or from malignancies. The purpose of this study was to evaluate the visibility of CRMO lesions in a whole-body diffusion-weighted imaging (WB-DWI) technique and its potential clinical value to better characterize MR-visible lesions.Material and MethodsWhole-body imaging at 3T was performed in 16 patients (average: 13 years) with confirmed CRMO. The protocol included 2D Short Tau Inversion Recovery (STIR) imaging in coronal and axial orientation as well as diffusion-weighted imaging in axial orientation. Visibility of lesions in DWI and STIR was evaluated by two readers in consensus. The apparent diffusion coefficient (ADC) was measured for every lesion and corresponding reference locations.ResultsA total of 33 lesions (on average 2 per patient) visible in STIR and DWI images (b = 800 s/mm2 and ADC maps) were included, predominantly located in the long bones. With a mean value of 1283 mm2/s in lesions, the ADC was significantly higher than in corresponding reference regions (782 mm2/s). By calculating the ratio (lesion to reference), 82% of all lesions showed a relative signal increase of 10% or higher and 76% (25 lesions) showed a signal increase of more than 15%. The median relative signal increase was 69%.ConclusionThis study shows that WB-DWI can be reliably performed in children at 3T and predominantly, the ADC values were substantially elevated in CRMO lesions. WB-DWI in conjunction with clinical data is seen as a promising technique to distinguish benign inflammatory processes (in terms of increased ADC values) from particular malignancies.

Highly Sensitive Hydrogen Gas Sensors Based on Gold Nanoparticle Decorated Zinc Oxide Nanosheets

Highly sensitive gold nanoparticle decorated zinc oxide nanosheet gas sensors have been fabricated using simple and rapid chemical methods capable of producing a normalised current gain of 2.54 (at 10V) in dry air containing 2.5ppm of hydrogen gas at 200C and a current gain of 382.53 under 125ppm. Compared to undecorated sheet based sensors where a response of 1.24 was observed under 125ppm at 200C a massive relative increase in signal is observed. The zinc oxide nanosheets are produced via a previously reported simple microwave assisted hydrothermal growth method and gold nanoparticles with mean diameter of 5nm synthesized via a simple sodium borohydride reduction of hydrogen tetrachloroaurate in the presence of polyvinylpyrrolidone (PVP) followed by drop casting onto a pre-patterned aluminium oxide substrate.

How the brain learns how few are “many”: An fMRI study of the flexibility of quantifier semantics

Previous work has shown that the meaning of a quantifier such as “many” or “few” depends in part on quantity. However, the meaning of a quantifier may vary depending on the context, e.g. in the case of common entities such as “many ants” (perhaps several thousands) compared to endangered species such as “many pandas” (perhaps a dozen). In a recent study (Heim et al., 2015 Front. Psychol.) we demonstrated that the relative meaning of “many” and “few” may be changed experimentally. In a truth value judgment task, displays with 40% of circles in a named color initially had a low probability of being labeled “many”. After a training phase, the likelihood of acceptance 40% as “many” increased. Moreover, the semantic learning effect also generalized to the related quantifier “few” which had not been mentioned in the training phase. Thus, fewer 40% arrays were considered “few.” In the present study, we tested the hypothesis that this semantic adaptation effect was supported by cytoarchitectonic Brodmann area (BA) 45 in Broca's region which may contribute to semantic evaluation in the context of language and quantification. In an event-related fMRI study, 17 healthy volunteers performed the same paradigm as in the previous behavioral study. We found a relative signal increase when comparing the critical, trained proportion to untrained proportions. This specific effect was found in left BA 45 for the trained quantifier “many”, and in left BA 44 for both quantifiers, reflecting the semantic adjustment for the untrained but related quantifier “few.” These findings demonstrate the neural basis for processing the flexible meaning of a quantifier, and illustrate the neuroanatomical structures that contribute to variable meanings that can be associated with a word when used in different contexts.

Study of dynamic contrast-enhanced characteristics of stage-I endometrial carcinomas versus polyps with 3.0 T MRI

To comparatively analyze the dynamic contrast-enhanced (DCE) characteristics and its clinical value between stage-I endometrial carcinomas versus polyps with 3.0T magnetic resonance imaging (MRI). A retrospective analysis was performed for DCE-MRI manifestation in 27 patients with histopathologically proved endometrial masses. There were stage-I endometrial carcinomas (n = 14) and polyps (n = 13). The signal intensity of solid component was measured and time-intensity curves (TIC) was obtained. TIC of lesions were divided into 4 subtypes. The time-to-peak (TTP) and signal intensity (SI) were determined from TICs. The arterial phase relative signal increase ratio (ARSIR), maximal relative signal increase ratio (MRSIR), signal enhancement ratio (SER) and signal intensity difference values (D) of each phase were calculated based on TIC curves respectively. The TIC of 14 stage-I endometrial carcinomas included type I (n = 4), type II (n = 6) and type IV (n = 4). The TIC of 13 polyps included type III (n = 3) and type IV (n = 10). The D values in each phase of 14 stage-I endometrial carcinomas were lower than normal muscle layers. There were statistic differences (P < 0.05) of each phase including 32, 48, 64, 109, 154, 199 s. For stage-I endometrial carcinomas, MRSIR and TTP were lower (P < 0.01) than normal muscle layers while SER was higher (P < 0.01) than normal muscle layers . The each phase of D of stage-I endometrial carcinomas were lower than polyps, and there were statistic differences (P < 0.05) of each phase including 32, 48, 64, 109, 154, 199 s. The MRSIR and TTP of stage-I endometrial carcinomas were lower (P < 0.01) than those of polyps while SER was higher (P < 0.01) than polyps. DCE-MRI can reflect enhanced features of stage-I endometrial carcinomas and polyps during different phases quantitatively. Parameters of DCE-MR and TIC are helpful in the diagnosis and differential diagnosis of stage-I endometrial carcinomas versus polyps.

Dynamic Contrast-Enhanced MRI of Cervical Cancers: Temporal Percentile Screening of Contrast Enhancement Identifies Parameters for Prediction of Chemoradioresistance

To systematically screen the tumor contrast enhancement of locally advanced cervical cancers to assess the prognostic value of two descriptive parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). This study included a prospectively collected cohort of 81 patients who underwent DCE-MRI with gadopentetate dimeglumine before chemoradiotherapy. The following descriptive DCE-MRI parameters were extracted voxel by voxel and presented as histograms for each time point in the dynamic series: normalized relative signal increase (nRSI) and normalized area under the curve (nAUC). The first to 100th percentiles of the histograms were included in a log-rank survival test, resulting in p value and relative risk maps of all percentile-time intervals for each DCE-MRI parameter. The maps were used to evaluate the robustness of the individual percentile-time pairs and to construct prognostic parameters. Clinical endpoints were locoregional control and progression-free survival. The study was approved by the institutional ethics committee. The p value maps of nRSI and nAUC showed a large continuous region of percentile-time pairs that were significantly associated with locoregional control (p < 0.05). These parameters had prognostic impact independent of tumor stage, volume, and lymph node status on multivariate analysis. Only a small percentile-time interval of nRSI was associated with progression-free survival. The percentile-time screening identified DCE-MRI parameters that predict long-term locoregional control after chemoradiotherapy of cervical cancer.

Dynamic contrast‐enhanced MR imaging for differentiation of rounded atelectasis from neoplasm

To characterize rounded atelectasis (RA) with dynamic contrast-enhanced MRI in the differential diagnosis of solitary peripheral pulmonary neoplasm. Twenty-four patients with diagnostically equivocal peripheral pulmonary nodules were examined with dynamic contrast-enhanced MRI. 13 patients had a total of 16 rounded atelectases and 11 had a neoplasm. The final diagnosis was made either by histology (n = 14) or follow-up examinations of at least 24 months (n = 10). The peripheral nodules were evaluated concerning their morphology and contrast-enhancement dynamics. Curves for signal intensity (SI) versus time were produced and the relative increase in SI, slope of SI during wash-in, and slope of SI during wash-out calculated. Additionally, SI time curves were evaluated using a two compartment model where the ratio for the SI of the fast and the slow component were calculated. Mean values from different tissues of interest were compared by an unpaired two-sided t-test. Analysis of the SI-time curves of the RAs revealed a curve shape similar to the pulmonary artery, but a magnitude in SI between artery and normal lung tissue. Linear curve fit showed a significantly steeper slope during wash-in and wash-out, and higher relative signal increase in atelectases as compared to neoplasms. Results from the two compartment model showed increased flow and a high ratio of the slow to the fast components with a long mean transit time in neoplasms. Three parameters, slope of SI during wash-in and wash-out, and the slow/fast ratio can be used as diagnostic tools for discrimination of RA and neoplasm.

Blood oxygen level-dependent magnetic resonance imaging using T2-prepared steady-state free-precession imaging in comparison to contrast-enhanced myocardial perfusion imaging

Diagnosis of inducible myocardial ischemia is important for deciding further diagnosis and therapy in coronary artery disease (CAD). Blood oxygen level-dependent (BOLD) cardiac magnetic resonance imaging (CMR) is a potential method to evaluate myocardial perfusion reserve alternatively to first-pass perfusion using contrast agents. We imaged 46 patients with suspected CAD on a 1.5 T whole-body CMR scanner using a T2-prepared steady-state free-precession (SSFP) BOLD-sensitive sequence and a SSFP-based first-pass sequence. All patients were scanned during rest and after 3 min of adenosine infusion (140 µg/kg/min). For myocardial first-pass visualization 0.1 mmol/kg Gadolinium-based contrast agent was used. In 90 myocardial segments a first-pass perfusion deficit could be seen. Relative BOLD signal increase was significantly lower in patients with perfusion deficits compared to patients without perfusion deficits (p < 0.0001). Patients with non-transmural and with transmural first-pass perfusion deficit also differed significantly for BOLD signal increase (p < 0.0001). ROC analysis showed an area under the curve of 0.83 for the T2-prepared SSFP sequence regarding detection of inducible perfusion deficit. T2-prepared BOLD imaging allows for visualization of myocardial perfusion reserve in a clinical setting without additional use of contrast agents.

Differential effects of eyes open or closed in darkness on brain activation patterns in blind subjects

In functional brain imaging, specific task conditions can be compared to a reference condition which is often eyes-open or eyes-closed in darkness without the execution of a specific task. Previous fMRI studies in sighted subjects have shown that eyes-open in darkness, without visual stimulation, increases the relative activity in cortical ocular motor and attentional areas (“exteroceptive” state; contrast OPEN > CLOSED). By contrast, eyes-closed causes a relative signal increase in sensory systems (“interoceptive” state; contrast CLOSED > OPEN). In the present study we used fMRI to determine whether these differential brain activity states can also be found in congenitally blind subjects: there were intragroup differences between the OPEN and CLOSED conditions. These differences were, however, less pronounced and occurred in other areas than in sighted controls. The contrast OPEN > CLOSED revealed a relative signal increase in the left frontal eye field, the middle occipital gyrus bilaterally and in the anterior cingulum. Relative signal increases in occipital cortex areas and the anterior cingulum were also apparent for this contrast in the intergroup comparison (congenitally totally blind subjects vs. sighted controls). They reflect the increased attentional load or arousal during the eyes-open condition and could be indicative of a functional reorganization of the occipital cortex in the blind. The contrast CLOSED > OPEN in the congenitally totally blind subjects lead to relative activations in the somatosensory cortex bilaterally, the middle temporal gyrus on the left and the frontal gyri on the right. These activations are residues of the “interoceptive” state found in sighted controls.

Tunable Enhancement of High Harmonic Emission from Laser Solid Interactions

Coherent wake emission is a unique source of extreme ultraviolet radiation and has been recently shown to provide the basis for intense attosecond light. Here we present a novel scheme, supported by particle-in-cell simulations, demonstrating that enhancement and spectral control of the coherent wake emission signal can be achieved by modifying the interaction plasma density ramp. Significant tunable enhancement of harmonic emission is verified experimentally, with factors of >50 in relative signal increase achieved in a narrow band of harmonics at the cutoff frequency.

Establishment of liver fibrosis in rabbit model and quantitative study on hepatic perfusion with dynamic whole-liver 3D MR imaging

To investigate the ideal approach in creating rabbit model of hepatic fibrosis and to evaluate the feasibility and value of dynamic whole-liver 3D magnetic resonance (MR) perfusion-weighted imaging (PWI) in the quantitative study on the staging of hepatic fibrosis. Rabbit model of hepatic fibrosis was created by intraperitoneal injection of 5% and 100% carbon tetrachloride (0.1 ml/kg, once a week) respectively. MR perfusion weighted imaging was performed at the 6th, 8th, 10th and 12th week since injection. The time of peak (TOP), the time to peak (TTP), the maximum slope of increase(MSI) and the maximal relative signal increase (MRSI) of portal vein and hepatic parenchyma were analyzed quantitatively, and were compared with pathological results. Comparison of different concentrations of CCl4 was analyzed using chi-square test. Inter-group comparison of perfusion parameters was analyzed using one-way ANOVA P less than 0.05 was regarded as statistically significant. 40% of the rabbits treated with 5% carbon tetrachloride developed hepatic fibrosis, while 75% of the rabbits treated with 100% carbon tetrachloride developed hepatic fibrosis; the mortality rate is significantly different between these two groups (X2=5.013, P less than 0.05). PWI examination was successfully achieved in 31 rabbits, liver perfusion baseline was stable, and good TIC curve was obtained. With the progress of hepatic fibrosis, TOP and TTP of portal vein and hepatic parenchyma were increased, and MSI and MRSI were decreased. There were significant differences among stage of S0-S2, S3 and S4. The method (100% carbon tetrachloride intraperitoneal injection, 0.1 ml/kg, once a week) has high success rate of creating rabbit model of hepatic fibrosis. The stage of hepatic fibrosis could be evaluated quantitatively with dynamic whole-liver 3D MR perfusion-weighted imaging.

Influence of oxygen and carbogen breathing on renal oxygenation measured by T2*‐weighted imaging at 3.0 T

The aim of the study was to assess the influence of carbogen (95% O(2), 5% CO(2)) or pure oxygen breathing on renal oxygenation measured by blood oxygenation level dependent (BOLD) magnetic resonance imaging at 3.0 T. Seven healthy young volunteers (median age 25, range 23-35 years) participated in the study. A T2*-weighted fat-saturated spoiled gradient-echo sequence was implemented on a 3.0 T whole-body imager (TE/TR = 27.9 ms/49 ms, excitation angle 20 degrees ) with an acquisition time of approximately 5.3 s. A total of 100 images were acquired during 22 min. A block design was applied for gas administration: 4 min room air, 4 min carbogen/oxygen, 4 min room air, 4 min carbogen/oxygen and 6 min room air. A compartment model was fitted to the data sets accounting for time-dependent increase/decrease of renal oxygenation as well as baseline changes of the scanner. T2*-weighted images showed good image quality without notable artefacts or distortions. Mean relative signal increase due to carbogen breathing was 2.73% (95% confidence interval: 1.34-5.54) in the right kidney and 3.76% (1.53-9.20) in the left kidney, while oxygen breathing led to a signal enhancement of 3.20% (2.57-3.98) in the right kidney and 3.16% (1.83-5.45) in the left kidney. No statistical difference was found between carbogen and oxygen breathing or between the oxygenation of the right and the left kidney. A significant difference was found in the characteristic time constant for the signal increase with a faster saturation taking place for oxygen breathing. Renal tissue oxygenation is clearly influenced by carbogen or oxygen breathing. The changes can be assessed by T2*-weighted MRI at high field strengths. The effects are in the expected range for the BOLD effect of 3-4% at 3.0 T. The proposed technique might be interesting for the assessment of renal tissue oxygenation and its regulation in patients with kidney diseases.

The resting brain in blind subjects – an fMRI study with eyes open and closed in darkness

Objective: It has been shown in normal subjects that opening the eyes in darkness without external visual stimulation increases activity in the ocular motor and attentional systems. By contrast, closing the eyes causes a relative signal increase in multiple sensory areas such as the visual, somatosensory, vestibular, auditory, and gustatory cortical areas. These two states of „resting“ activity of the human brain in complete darkness, which can be imaged using fMRI, were termed the „exteroceptive“ state (contrast OPEN>CLOSED) and the „interoceptive“ state (contrast CLOSED>OPEN). In the present study we investigated whether similar brain activity states can be found in blind subjects when opening and closing their eyes. Methods: Seven congenitally, totally blind individuals participated in the study. Subjects were trained outside the scanner to perform the following tasks: eyes open (OPEN) or eyes closed (CLOSED) at rest while looking straight ahead in complete darkness. Functional images were acquired on a 1.5 T standard clinical scanner using echo-planar imaging. The data were compared to data published earlier of a matched group of healthy volunteers (Marx et al. 2003). Analysis was performed using SPM2. Results: Overall, the differences between the OPEN and CLOSED conditions were less pronounced in the blind subjects than in the controls. In congenitally, totally blind subjects the contrast OPEN>CLOSED revealed a relative increase in activity in the middle occipital gyrus bilaterally as well as in the anterior cingulate cortex. The intergroup comparison (congenitally, totally blind subjects vs. controls) for this contrast showed an activity increase in regions similar to those found in the blind subjects alone. Discussion: There are also differences in brain activity patterns between eyes-open or eyes-closed at rest in congenitally, totally blind subjects, but they are not those of the above-described „intero-“/“exteroceptive“ states. They are rather diametrically opposed to those observed in sighted controls: the activity increases in the occipital cortex for the contrast OPEN>CLOSED suggest a functional reorganization of the visual cortex. While the visual cortex has been previously shown to mediate attentional tasks in congenitally blind subjects, its activation during the eyes-open condition in conjunction with the anterior cingulate might be indicative of an increased attentional load.

Non‐invasive analysis of cell cycle dynamics in single living cells with Raman micro‐spectroscopy

Raman micro-spectroscopy is a laser-based technique which enables rapid and non-invasive biochemical analysis of cells and tissues without the need for labels, markers or stains. Previous characterization of the mammalian cell cycle using Raman micro-spectroscopy involved the analysis of suspensions of viable cells and individual fixed and/or dried cells. Cell suspensions do not provide cell-specific information, and fixing/drying can introduce artefacts which distort Raman spectra, potentially obscuring both qualitative and quantitative analytical results. In this article, we present Raman spectral characterization of biochemical changes related to cell cycle dynamics within single living cells in vitro. Raman spectra of human osteosarcoma cells synchronized in G(0)/G(1), S, and G(2)/M phases of the cell cycle were obtained and multivariate statistics applied to analyze the changes in cell spectra as a function of cell cycle phase. Principal components analysis identified spectral differences between cells in different phases, indicating a decrease in relative cellular lipid contribution to Raman spectral signatures from G(0)/G(1) to G(2)/M, with a concurrent relative increase in signal from nucleic acids and proteins. Supervised linear discriminant analysis of spectra was used to classify cells according to cell cycle phase, and exhibited 97% discrimination between G(0)/G(1)-phase cells and G(2)/M-phase cells. The non-invasive analysis of live cell cycle dynamics with Raman micro-spectroscopy demonstrates the potential of this approach to monitoring biochemical cellular reactions and processes in live cells in the absence of fixatives or labels.

Improved T1-weighted dynamic contrast-enhanced MRI to probe microvascularity and heterogeneity of human glioma

Dynamic contrast-enhanced (DCE) T(1)-weighted magnetic resonance imaging (MRI) is a powerful tool capable of providing quantitative assessment of contrast uptake and characterization of microvascular structure in human gliomas. The kinetics of the bolus injection doped with increasing concentrations of gadopentate dimeglumine (Gd-DTPA) depends on tissue as well as pulse sequence parameters. A simple method is described that overcomes the limitation of relative signal increase measurement and may lead to improved accuracy in quantification of perfusion indices of glioma. Based on an analysis of the contrast behavior of spoiled gradient-recalled echo sequence; a parameter K with arbitrary unit 5.0 is introduced, which provides a better approximation to the differential T(1) relaxation rate. DCE-MRI measurements of relative cerebral blood volume (rCBV) and cerebral blood flow (rCBF) were calculated in 25 patients with brain tumors (15=high-grade glioma, 10=low-grade glioma). The mean rCBV was 6.46 +/- 2.45 in high-grade glioma and 2.89 +/- 1.47 in the low-grade glioma. The rCBF was 3.94 +/- 1.47 in high-grade glioma while 2.25 +/- 0.87 in low-grade glioma. A significant difference in rCBF and rCBV was found between high- and low-grade gliomas. This simple and robust technique reveals the complexity of tumor vasculature and heterogeneity that may aid in therapeutic management especially in nonenhancing high-grade gliomas. We conclude that the precontrast medium steady-state residue parameter K may be useful in improved quantification of perfusion indices in human glioma using T(1)-weighted DCE-MRI.