We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing ele

Transcriptional profiling of lung adenocarcinomas has identified numerous gene expression phenotype (GEP) and risk prediction (RP) signatures associated with patient outcome. However, classification agreement between signatures, underlying transcriptional programs, and independent signature validation are less studied. We classified 2395 transcriptional adenocarcinoma profiles, assembled from 17 p

Pulmonary diseases are known to be largely inhomogeneous. To evaluate such inhomogeneities, we are testing an image-based method to measure gas flow in the lung regionally. Dynamic, spin-density-weighted hyperpolarized (3)He MR images performed during slow inhalation of this gas were analyzed to quantify regional inflation rate. This parameter was measured in regions of interest (ROIs) that were d

In preclinical research, allergic asthma is investigated in rats sensitised with the antigen ovalbumin (OVA), followed by a challenge with aerosolised OVA to induce an inflammatory reaction of the lower airways. This causes diffuse, nonfocal ventilation defects that lead to heterogeneously distributed signal intensities in hyperpolarised (HP) (3)He MR images, which are difficult to assess directly

We have developed over the past years an experimental magnetic resonance imaging (MRI) and polarized gases compatible mechanical respirator for the study of the small experimental animal. The respirator has been successfully used for experiments both in the MRI setting for polarized (3)He, (19)F, and proton imaging as well as for functional measurements of the lungs. The new main pneumatic valve w

INTRODUCTION: Proton (¹H ) magnetic resonance imaging (MRI) can be utilized to quantify pulmonary edema in endotoxin-induced pulmonary inflammation and hyperpolarized (HP) ³He MRI can assess pulmonary ventilation. Neither of the methods has been applied to assess the impact of a drug on endotoxin-induced pulmonary inflammation in vivo. The aim of the current study was to evaluate the capability of

PURPOSE: To evaluate the lipopolysaccharide (LPS) model of chronic obstructive pulmonary disease (COPD) in mouse with (1)H and hyperpolarized (HP) (3)He MR imaging.MATERIALS AND METHODS: Axial slices of the lung volume were acquired with HP (3)He and (1)H MRI at 4, 24, and 48 h after LPS exposure. A quantitative ventilation index was calculated from two HP (3)He acquisitions. A bronchoalveolar lav

The aim of this study was to investigate if a rapid magnetic resonance imaging (MRI) screening protocol (

PURPOSE: To evaluate whether MRI signal and T2* measurements of lung tissue acquired at ultrashort detection times (tds) can detect emphysematous changes in lungs.MATERIALS AND METHODS: MR signal intensity of in vivo mouse lungs was measured at 4.7 T at tds of 0.2 and 0.4 msec using single-point imaging (SPI). T2* was calculated from the measurements obtained at the two tds. Two groups of 8- and 3

PURPOSE: To develop a multiplanar magnetic resonance temperature imaging (MRTI) technique based on interleaved gradient-echo echo-planar imaging (EPI), verify in phantom, develop software tools to process and display data on a clinical scanner in near real-time, and demonstrate feasibility to monitor ultrasound thermal ablation therapy in vivo.MATERIALS AND METHODS: Temperature estimation used com

The influence of flip angle and flow velocity on the signal intensity achieved when imaging a hyperpolarized substance with a spoiled gradient echo sequence was investigated. The study was performed both theoretically and experimentally using hyperpolarized xenon dissolved in ethanol. Analytical expressions regarding the optimal flip angle with respect to signal and the corresponding signal level

PURPOSE: The feasibility of hyperpolarized 129Xe for fast MR angiography (MRA) was evaluated using the echo-planar imaging (EPI) technique.MATERIAL AND METHODS: Hyperpolarized Xe gas was dissolved in ethanol, a carrier agent with high solubility for Xe (Ostwald solubility coefficient 2.5) and long relaxation times. The dissolved Xe was injected as a bolus into a flow phantom where the mean flow ve

PURPOSE: To study the feasibility of an interleaved gradient-echo, echo-planar imaging (iGE-EPI) sequence for multiplanar magnetic resonance temperature imaging (MRTI) to monitor intracerebral thermal treatment three-dimensionally using multielement ultrasound applicators.MATERIALS AND METHODS: Transmissible venereal tumor (TVT) fragments were injected into the right cerebral hemisphere of five do

In 3-D contrast-enhanced magnetic resonance (MR) angiography of the lower extremities the goal is most often to enhance arterial structures while keeping veins and surrounding tissue unenhanced. Imaging during steady-state concentration of a blood pool agent or during poor timing of an extra-cellular contrast medium may result in simultaneous venous enhancement, making interpretation of the angiog

PURPOSE: To evaluate MRI-based techniques for visual guidance, thermal monitoring, and assessment during transurethral ultrasound thermal therapy of implanted tumors in an in vivo canine prostate model.MATERIALS AND METHODS: Transmissible venereal tumors (TVT) were grown in the right lobe of the prostate in four dogs. High-temperature thermal therapy was selectively applied to the tumor-bearing lo

The negatively charged contrast agent Gd-DTPA2- distributes inversely to the cartilage fixed charged density. This enables structural cartilage examinations by contrast-enhanced MRI. In line with the development of a clinically applicable protocol for such examinations, this study describes the temporal pattern of Gd-DTPA2- distribution in femoral knee cartilage at three different doses in healthy

Magnetic response image plane nonuniformity and stochastic noise are properties that greatly influence the outcome of quantitative magnetic resonance imaging (MRI) evaluations such as gel dosimetry measurements using MRI. To study these properties, robust and accurate image analysis methods are required. New nonuniformity level assessment methods were designed, since previous methods were found to

A safe and reproducible mixing procedure for the manufacture of a polymerization-based dosemeter gel evaluated using MRI (PoMRI) is presented. The dose response, obtained by irradiating gel-filled vials with absorbed doses in the interval 0-20 Gy and evaluated with respect to 1/T2, was found to be linear in the interval 0-8 Gy, with a sensitivity of 0.211 s-1Gy-1 (r2 = 0.998) at 1.5 T. Evaluation

MR image nonuniformity can vary significantly with the spin-echo pulse sequence repetition time. When MR images with different nonuniformity shapes are used in a T1-calculation the resulting T1-image becomes nonuniform. As shown in this work the uniformity TR-dependence of the spin-echo pulse sequence is a critical property for T1 measurements in general and for ferrous sulfate dosimeter gel (FeGe

A method for analysing and comparing treatment planning system (TPS) data and ferrous dosimeter gel measurements evaluated with MRI (FeMRI) was developed, including image processing to final absorbed dose images. Measurements were analysed according to this method and FeMRI data were thereby compared with the TPS-calculated dose distribution. For photons, differences between FeMRI- and TPS dose da