CluF: an unsupervised iterative cluster-fusion method for patient stratification using multiomics data.

Motivation: Patient stratification is crucial for the effective treatment or management of heterogeneous diseases, including cancers. Multiomic technologies facilitate molecular characterization of human diseases; however, the complexity of data warrants the need for the development of robust data integration tools for patient stratification using machine-learning approaches.

Results: CluF iteratively integrates three types of multiomic data (mRNA, miRNA, and DNA methylation) using pairwise patient similarity matrices built from each omic data.

Endothelin-axis antagonism enhances tumor perfusion in pancreatic cancer.

Delivery of therapeutic agents in pancreatic cancer (PC) is impaired due to its hypovascular and desmoplastic tumor microenvironment. The Endothelin (ET)-axis is the major regulator of vasomotor tone under physiological conditions and is highly upregulated in multiple cancers. We investigated the effect of dual endothelin receptor antagonist bosentan on perfusion and macromolecular transport in a PC cell-fibroblast co-implantation tumor model using Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI).

Knee joint unloading and daily physical activity associate with cartilage T2 relaxation times 1 month after ACL injury.

Osteoarthritis (OA) is prevalent after anterior cruciate ligament (ACL) injury, but mechanismsunderlying its development are poorly understood. The purpose of this study was to determine if gait biomechanics and daily physical activity (PA) associate with cartilage T2 relaxation times, a marker of collagen organization and water content, 1 month after ACL injury. Twenty-seven participants (15-35 years old) without chondral lesions completed magnetic resonance imaging, three-dimensional gait analysis, and 1 week of PA accelerometry.

Multimodal Theranostic Nanoformulations Permit Magnetic Resonance Bioimaging of Antiretroviral Drug Particle Tissue-Cell Biodistribution.

Rationale: Long-acting slow effective release antiretroviral therapy (LASER ART) was developed to improve patient regimen adherence, prevent new infections, and facilitate drug delivery to human immunodeficiency virus cell and tissue reservoirs. In an effort to facilitate LASER ART development, "multimodal imaging theranostic nanoprobes" were created. These allow combined bioimaging, drug pharmacokinetics and tissue biodistribution tests in animal models.

Multimodal Imaging Nanoparticles Derived from Hyaluronic Acid for Integrated Preoperative and Intraoperative Cancer Imaging.

Surgical resection remains the most promising treatment strategy for many types of cancer. Residual malignant tissue after surgery, a consequence in part due to positive margins, contributes to high mortality and disease recurrence. In this study, multimodal contrast agents for integrated preoperative magnetic resonance imaging (MRI) and intraoperative fluorescence image-guided surgery (FIGS) are developed.

Development of europium doped core-shell silica cobalt ferrite functionalized nanoparticles for magnetic resonance imaging.

Unlabelled: The size, shape and chemical composition of europium (Eu) cobalt ferrite (CFEu) nanoparticles were optimized for use as a "multimodal imaging nanoprobe" for combined fluorescence and magnetic resonance bioimaging. Doping Eu ions into a CF structure imparts unique bioimaging and magnetic properties to the nanostructure that can be used for real-time screening of targeted nanoformulations for tissue biodistribution assessment. The CFEu nanoparticles (size ∼7.

Age-related changes in cerebellar and hypothalamic function accompany non-microglial immune gene expression, altered synapse organization, and excitatory amino acid neurotransmission deficits.

We describe age-related molecular and neuronal changes that disrupt mobility or energy balance based on brain region and genetic background. Compared to young mice, aged C57BL/6 mice exhibit marked locomotor (but not energy balance) impairments. In contrast, aged BALB mice exhibit marked energy balance (but not locomotor) impairments.

Polyplex-mediated inhibition of chemokine receptor CXCR4 and chromatin-remodeling enzyme NCOA3 impedes pancreatic cancer progression and metastasis.

Pancreatic cancer (PC) is one of the most aggressive malignancies due to intense desmoplasia, extreme hypoxia and inherent chemoresistance. Studies have implicated the expression of chemokine receptor CXCR4 and nuclear receptor co-activator-3 (NCOA3) in the development of desmoplasia and metastatic spread of PC. Using a series of polymeric CXCR4 antagonists (PCX), we optimized formulation of PCX/siNCOA3 polyplexes to simultaneously target CXCR4 and NCOA3 in PC.

Generation and Disease Model Relevance of a Manganese Enhanced Magnetic Resonance Imaging-Based NOD/scid-IL-2Rγc(null) Mouse Brain Atlas.

Strain specific mouse brain magnetic resonance imaging (MRI) atlases provide coordinate space linked anatomical registration. This allows longitudinal quantitative analyses of neuroanatomical volumes and imaging metrics for assessing the role played by aging and disease to the central nervous system. As NOD/scid-IL-2Rγ(c)(null) (NSG) mice allow human cell transplantation to study human disease, these animals are used to assess brain morphology.

Manganese-Enhanced Magnetic Resonance Imaging Reflects Brain Pathology During Progressive HIV-1 Infection of Humanized Mice.

Progressive human immunodeficiency viral (HIV) infection commonly leads to a constellation of cognitive, motor, and behavioral impairments. These are collectively termed HIV-associated neurocognitive disorders (HAND). While antiretroviral therapy (ART) reduces HAND severity, it does not affect disease prevalence.

Small magnetite antiretroviral therapeutic nanoparticle probes for MRI of drug biodistribution.

Aim: Drug toxicities, compliance and penetrance into viral reservoirs have diminished the efficacy of long-term antiretroviral therapy (ART) for treatment of HIV infection. Cell-targeted nanoformulated ART was developed to improve disease outcomes. However, rapid noninvasive determination of drug biodistribution is unrealized.

Mouse brain fixation to preserve In vivo manganese enhancement for ex vivo manganese-enhanced MRI.

Purpose: To develop a tissue fixation method that preserves in vivo manganese enhancement for ex vivo magnetic resonance imaging (MRI). The needs are clear, as conventional in vivo manganese-enhanced MRI (MEMRI) applied to live animals is time-limited, hence limited in spatial resolution and signal-to-noise ratio (SNR). Ex vivo applications can achieve superior spatial resolution and SNR through increased signal averaging and optimized radiofrequency coil designs.

Landmark optimization using local curvature for point-based nonlinear rodent brain image registration.

Purpose. To develop a technique to automate landmark selection for point-based interpolating transformations for nonlinear medical image registration. Materials and Methods.

Proton magnetic resonance spectroscopy in multiple sclerosis.

Proton magnetic resonance spectroscopy ((1)H-MRS) provides tissue metabolic information in vivo. This article reviews the role of MRS-determined metabolic alterations in lesions, normal-appearing white matter, gray matter, and spinal cord in advancing our knowledge of pathologic changes in multiple sclerosis (MS). In addition, the role of MRS in objectively evaluating therapeutic efficacy is reviewed.

Volume and shape in feature space on adaptive FCM in MRI segmentation.

Intensity non-uniformity (bias field) correction, contextual constraints over spatial intensity distribution and non-spherical cluster's shape in the feature space are incorporated into the fuzzy c-means (FCM) for segmentation of three-dimensional multi-spectral MR images. The bias field is modeled by a linear combination of smooth polynomial basis functions for fast computation in the clustering iterations. Regularization terms for the neighborhood continuity of either intensity or membership are added into the FCM cost functions.

Generalized fuzzy clustering for segmentation of multi-spectral magnetic resonance images.

An integrated approach for multi-spectral segmentation of MR images is presented. This method is based on the fuzzy c-means (FCM) and includes bias field correction and contextual constraints over spatial intensity distribution and accounts for the non-spherical cluster's shape in the feature space. The bias field is modeled as a linear combination of smooth polynomial basis functions for fast computation in the clustering iterations.

Segmentation of gadolinium-enhanced lesions on MRI in multiple sclerosis.

Purpose: To develop and implement a method for identification and quantification of gadolinium (Gd) enhancements with minimal human intervention.

Materials And Methods: Dual fast spin echo (FSE), fluid attenuation inversion recovery (FLAIR), and pre- and postcontrast T1-weighted spin echo were acquired on 22 subjects. The enhancements were identified on the postcontrast T1-weighted images based on morphological operations.

Fast quantification of proton magnetic resonance spectroscopic imaging with artificial neural networks.

Accurate quantification of the MRSI-observed regional distribution of metabolites involves relatively long processing times. This is particularly true in dealing with large amount of data that is typically acquired in multi-center clinical studies. To significantly shorten the processing time, an artificial neural network (ANN)-based approach was explored for quantifying the phase corrected (as opposed to magnitude) spectra.

Unified approach for multiple sclerosis lesion segmentation on brain MRI.

The presence of large number of false lesion classification on segmented brain MR images is a major problem in the accurate determination of lesion volumes in multiple sclerosis (MS) brains. In order to minimize the false lesion classifications, a strategy that combines parametric and nonparametric techniques is developed and implemented. This approach uses the information from the proton density (PD)- and T2-weighted and fluid attenuation inversion recovery (FLAIR) images.

Implementation of high-dimensional feature map for segmentation of MR images.

A method that considerably reduces the computational and memory complexities associated with the generation of high-dimensional (> or =3) feature maps for image segmentation is described. The method is based on the K-nearest neighbor (KNN) classification and consists of two parts: preprocessing of feature space and fast KNN. This technique is implemented on a PC and applied for generating 3D and 4D feature maps for segmenting MR brain images of multiple sclerosis patients.

Segmentation and quantification of black holes in multiple sclerosis.

A technique that involves minimal operator intervention was developed and implemented for identification and quantification of black holes on T1-weighted magnetic resonance images (T1 images) in multiple sclerosis (MS). Black holes were segmented on T1 images based on grayscale morphological operations. False classification of black holes was minimized by masking the segmented images with images obtained from the orthogonalization of T2-weighted and T1 images.