Rapid in vivo Taxotere quantitative chemosensitivity response by 4.23 Tesla sodium MRI and histo-immunostaining features in N-Methyl-N-Nitrosourea induced breast tumors in rats

BACKGROUND: Sodium weighted images can indicate sodium signal intensities from different features in the tumor before and 24 hours following administration of Taxotere. AIM: To evaluate the association of in vivo intracellular sodium magnetic resonance image intensities with immuno-biomarkers and histopathological features to monitor the early tumor response to Taxotere chemotherapy in Methyl-Nitroso-Urea induced rat xenograft breast tumors. METHODS AND MATERIALS: Methyl-Nitroso-Urea (MNU) induced rat xenograft breast tumors were imaged for sodium MRI and compared with tumor histology, immunostaining after 24 hours chemotherapy. RESULTS: Sodium MRI signal intensities represented sodium concentrations. Excised tumor histological sections showed different in vitro histological end points i.e. single strand DNA content of cell nuclei during cell cycle (G1/S-G2/M), distinct S or M histograms (Feulgen labeling to nuclear DNA content by CAS 200), mitotic figures and apoptosis at different locations of breast tumors. Necrosis and cystic fluid appeared gray on intracellular (IC) sodium images while apoptosis rich regions appeared brighter on IC sodium images. After 24 hours Taxotere-treated tumors showed lower 'IC/EC ratio' of viable cells (65–76%) with higher mitotic index; apoptotic tumor cells at high risk due to cytotoxicity (>70% with high apoptotic index); reduced proliferation index (270 vs 120 per high power field) associated with enhanced IC sodium in vivo MR image intensities and decreased tumor size (3%; p < 0.001; n = 16) than that of pre-treated tumors. IC-Na MR signal intensities possibly indicated Taxotere chemosensitivity response in vivo associated with apoptosis and different pre-malignant features within 24 hours of exposure of cancer cells to anti-neoplastic Taxotere drug. CONCLUSION: Sodium MRI imaging may be used as in vivo rapid drug monitoring method to evaluate Taxotere chemosensitivity response associated with neoplasia, apoptosis and tumor histology features

Combined MR Data Acquisition of Multicontrast Images Using Variable Acquisition Parameters and K-Space Data Sharing

A new technique to reduce clinical magnetic resonance imaging (MRI) scan time by varying acquisition parameters and sharing k-space data between images, is proposed. To improve data utilization, acquisition of multiple images of different contrast is combined into a single scan, with variable acquisition parameters including repetition time (TR), echo time (TE), and echo train length (ETL). This approach is thus referred to as a "combo acquisition." As a proof of concept, simulations of MRI experiments using spin echo (SE) and fast SE (FSE) sequences were performed based on Bloch equations. Predicted scan time reductions of 25%-50% were achieved for 2-contrast and 3-contrast combo acquisitions. Artifacts caused by nonuniform k-space data weighting were suppressed through semi-empirical optimization of parameter variation schemes and the phase encoding order. Optimization was assessed by minimizing three quantitative criteria: energy of the "residue point spread function (PSF)," energy of "residue profiles" across sharp tissue boundaries, and energy of "residue images." In addition, results were further evaluated by quantitatively analyzing the preservation of contrast, the PSF, and the signal-to-noise ratio. Finally, conspicuity of lesions was investigated for combo acquisitions in comparison with standard scans. Implications and challenges for the practical use of combo acquisitions are discussed

MRI Scan Time Reduction through K-Space Data Sharing in Combo Acquisitions with a Spin Echo Sequence

We propose a technique to reduce scan time for magnetic resonance imaging (MRI) through sharing of k-space data between images. As a proof of concept, we ran simulations of MRI experiments based on Bloch equations using a spin echo sequence. We generated images of a realistic brain phantom containing the tissues: white matter, gray matter, and cerebrospinal fluid. A set of k-space data was acquired while varying two acquisition parameters: repetition time (TR) and echo time (TE). This data set was then used to reconstruct multiple images of different contrast. Customized variation of TR and TE allowed us to obtain different contrast weightings of signal values. We present results for 2-contrast and 3-contrast "combo" acquisitions and compare them with images from acquisitions with fixed TR and TE. Scan time reductions of 30%-52% were achieved. Artifacts stemming from non-uniform and tissue-dependent data weighting in the Fourier domain were minimized through systematic optimization of the order of phase encoding and of variation schemes for TR and TE. No obvious degradation of image quality and resolution was observed. In addition, we quantitatively analyzed preservation of contrast, image profiles of sharp tissue boundaries, and signal-to-noise-ratio

Coarse-to-fine Kidney Segmentation Framework Incorporating with Abnormal Detection and Correction

In this work, we formulate this segmentation problem into two sub-task: 1) kidney segmentation 2) tumor segmentation. In the first task, three 2D CNN are used to separate the kidney(including tumor )region with background (two class segmentation). In the second task, one 3D CNN and one two channel 2D CNN are used to separate detect and refine tumor within a relative smaller image region

Discrimination Task Reveals Differences in Neural Bases of Tinnitus and Hearing Impairment

We investigated auditory perception and cognitive processing in individuals with chronic tinnitus or hearing loss using functional magnetic resonance imaging (fMRI). Our participants belonged to one of three groups: bilateral hearing loss and tinnitus (TIN), bilateral hearing loss without tinnitus (HL), and normal hearing without tinnitus (NH). We employed pure tones and frequency-modulated sweeps as stimuli in two tasks: passive listening and active discrimination. All subjects had normal hearing through 2 kHz and all stimuli were low-pass filtered at 2 kHz so that all participants could hear them equally well. Performance was similar among all three groups for the discrimination task. In all participants, a distributed set of brain regions including the primary and non-primary auditory cortices showed greater response for both tasks compared to rest. Comparing the groups directly, we found decreased activation in the parietal and frontal lobes in the participants with tinnitus compared to the HL group and decreased response in the frontal lobes relative to the NH group. Additionally, the HL subjects exhibited increased response in the anterior cingulate relative to the NH group. Our results suggest that a differential engagement of a putative auditory attention and short-term memory network, comprising regions in the frontal, parietal and temporal cortices and the anterior cingulate, may represent a key difference in the neural bases of chronic tinnitus accompanied by hearing loss relative to hearing loss alone

Calibrationless Reconstruction of Uniformly-Undersampled Multi-Channel MR Data with Deep Learning Estimated ESPIRiT Maps

Purpose: To develop a truly calibrationless reconstruction method that derives ESPIRiT maps from uniformly-undersampled multi-channel MR data by deep learning. Methods: ESPIRiT, one commonly used parallel imaging reconstruction technique, forms the images from undersampled MR k-space data using ESPIRiT maps that effectively represents coil sensitivity information. Accurate ESPIRiT map estimation requires quality coil sensitivity calibration or autocalibration data. We present a U-Net based deep learning model to estimate the multi-channel ESPIRiT maps directly from uniformly-undersampled multi-channel multi-slice MR data. The model is trained using fully-sampled multi-slice axial brain datasets from the same MR receiving coil system. To utilize subject-coil geometric parameters available for each dataset, the training imposes a hybrid loss on ESPIRiT maps at the original locations as well as their corresponding locations within the standard reference multi-slice axial stack. The performance of the approach was evaluated using publicly available T1-weighed brain and cardiac data. Results: The proposed model robustly predicted multi-channel ESPIRiT maps from uniformly-undersampled k-space data. They were highly comparable to the reference ESPIRiT maps directly computed from 24 consecutive central k-space lines. Further, they led to excellent ESPIRiT reconstruction performance even at high acceleration, exhibiting a similar level of errors and artifacts to that by using reference ESPIRiT maps. Conclusion: A new deep learning approach is developed to estimate ESPIRiT maps directly from uniformly-undersampled MR data. It presents a general strategy for calibrationless parallel imaging reconstruction through learning from coil and protocol specific data

Magnetic resonance spectroscopy reveals N-acetylaspartate reduction in hippocampus and cingulate cortex after fear conditioning

a b s t r a c t The fear conditioning in rodents provides a valuable translational tool to investigate the neural basis of learning and memory and potentially the neurobiology of post-traumatic stress disorder (PTSD). Neurobiological changes induced by fear conditioning have largely been examined ex vivo while progressive &apos;real-time&apos; changes in vivo remain under-explored. Single voxel proton magnetic resonance spectroscopy ( 1 H MRS) of the hippocampus, cingulate cortex and thalamus of adult male C57BL/6N mice (N¼ 12) was performed at 1 day before, 1 day and 1 week after, fear conditioning training using a 7T scanner. N-acetylaspartate (NAA), a marker for neuronal integrity and viability, significantly decreased in the hippocampus at 1 day and 1 week post-conditioning. Significant NAA reduction was also observed in the cingulate cortex at 1 day post-conditioning. These findings of hippocampal NAA decrease indicate reduced neuronal dysfunction and/or neuronal integrity, contributing to the traumarelated PTSD-like symptoms. The neurochemical changes characterized by 1 H MRS can shed light on the biochemical mechanisms of learning and memory. Moreover, such information can potentially facilitate prompt intervention for patients with psychiatric disorders

PPAR? Downregulation by TGF in Fibroblast and Impaired Expression and Function in Systemic Sclerosis: A Novel Mechanism for Progressive Fibrogenesis

The nuclear orphan receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ) is expressed in multiple cell types in addition to adipocytes. Upon its activation by natural ligands such as fatty acids and eicosanoids, or by synthetic agonists such as rosiglitazone, PPAR-γ regulates adipogenesis, glucose uptake and inflammatory responses. Recent studies establish a novel role for PPAR-γ signaling as an endogenous mechanism for regulating transforming growth factor-ß (TGF-ß)- dependent fibrogenesis. Here, we sought to characterize PPAR-γ function in the prototypic fibrosing disorder systemic sclerosis (SSc), and delineate the factors governing PPAR-γ expression. We report that PPAR-γ levels were markedly diminished in skin and lung biopsies from patients with SSc, and in fibroblasts explanted from the lesional skin. In normal fibroblasts, treatment with TGF-ß resulted in a time- and dose-dependent down-regulation of PPAR-γ expression. Inhibition occurred at the transcriptional level and was mediated via canonical Smad signal transduction. Genome-wide expression profiling of SSc skin biopsies revealed a marked attenuation of PPAR-γ levels and transcriptional activity in a subset of patients with diffuse cutaneous SSc, which was correlated with the presence of a ''TGF-ß responsive gene signature'' in these biopsies. Together, these results demonstrate that the expression and function of PPAR-γ are impaired in SSc, and reveal the existence of a reciprocal inhibitory cross-talk between TGF-ß activation and PPAR-γ signaling in the context of fibrogenesis. In light of the potent anti-fibrotic effects attributed to PPAR-γ, these observations lead us to propose that excessive TGF-ß activity in SSc accounts for impaired PPAR-γ function, which in turn contributes to unchecked fibroblast activation and progressive fibrosis. © 2010 Wei et al

Fast Inhibition of Glutamate-Activated Currents by Caffeine

Background: Caffeine stimulates calcium-induced calcium release (CICR) in many cell types. In neurons, caffeine stimulates CICR presynaptically and thus modulates neurotransmitter release. Methodology/Principal Findings: Using the whole-cell patch-clamp technique we found that caffeine (20 mM) reversibly increased the frequency and decreased the amplitude of miniature excitatory postsynaptic currents (mEPSCs) in neocortical neurons. The increase in mEPSC frequency is consistent with a presynaptic mechanism. Caffeine also reduced exogenously applied glutamate-activated currents, confirming a separate postsynaptic action. This inhibition developed in tens of milliseconds, consistent with block of channel currents. Caffeine (20 mM) did not reduce currents activated by exogenous NMDA, indicating that caffeine block is specific to non-NMDA type glutamate receptors. Conclusions/Significance: Caffeine-induced inhibition of mEPSC amplitude occurs through postsynaptic block of non-NMDA type ionotropic glutamate receptors. Caffeine thus has both pre and postsynaptic sites of action at excitatory synapses