Development and Application of a Virtual Imaging Trial Framework for Longitudinal Quantification of Emphysema in CT.

Pulmonary emphysema is a progressive lung disease that requires accurate evaluation for optimal management. This task, possible using quantitative CT, is particularly challenging as scanner and patient attributes change over time, negatively impacting the CT-derived quantitative measures. Efforts to minimize such variations have been limited by the absence of ground truth in clinical data, thus necessitating reliance on clinical surrogates, which may not have one-to-one correspondence to CT-based findings.

Radiographic Imaging of Community-Acquired Pneumonia: A Case-Based Review.

The chest radiograph is the most common imaging examination performed in most radiology departments, and one of the more common indications for these studies is suspected infection. Radiologists must therefore be aware of less common radiographic patterns of pulmonary infection if they are to add value in the interpretation of chest radiographs for this indication. This review uses a case-based format to illustrate a range of imaging findings that can be associated with acute pulmonary infection and highlight findings that should prompt investigation for diseases other than community-acquired pneumonia to prevent misdiagnosis and delays in appropriate management.

Image quality of photon counting and energy integrating chest CT - Prospective head-to-head comparison on same patients.

Purpose: To prospectively compare the image quality of high-resolution, low-dose photon-counting detector CT (PCD-CT) with standard energy-integrating-detector CT (EID) on the same patients.

Method: IRB-approved, prospective study; patients received same-day non-contrast CT on EID and PCD-CT (NAEOTOM Alpha, blinded) with clinical protocols. Four blinded radiologists evaluated subsegmental bronchial wall definition, noise, and overall image quality in randomized order (0 = worst; 100 = best).

MR Imaging for the Evaluation of Diffuse Lung Disease: Where Are We?

Patients with diffuse lung diseases require thorough medical and social history and physical examinations, coupled with a multitude of laboratory tests, pulmonary function tests, and radiologic imaging to discern and manage the specific disease. This review summarizes the current state of imaging of various diffuse lung diseases by hyperpolarized MR imaging. The potential of hyperpolarized MR imaging as a clinical tool is outlined as a novel imaging approach that enables further understanding of the cause of diffuse lung diseases, permits earlier detection of disease progression before that found with pulmonary function tests, and can delineate physiologic response to lung therapies.

Noninvasive diagnosis of pulmonary hypertension with hyperpolarised Xe magnetic resonance imaging and spectroscopy.

Background: The diagnosis of pulmonary hypertension (PH) remains challenging. Pre- and post-capillary PH have different signatures on noninvasive Xe gas-exchange magnetic resonance imaging (MRI) and dynamic MR spectroscopy (MRS). We tested the accuracy of Xe MRI/MRS to diagnose PH status compared to right heart catheterisation (RHC).

Radiographic Imaging of Community-Acquired Pneumonia: A Case-Based Review.

The chest radiograph is the most common imaging examination performed in most radiology departments, and one of the more common indications for these studies is suspected infection. Radiologists must therefore be aware of less common radiographic patterns of pulmonary infection if they are to add value in the interpretation of chest radiographs for this indication. This review uses a case-based format to illustrate a range of imaging findings that can be associated with acute pulmonary infection and highlight findings that should prompt investigation for diseases other than community-acquired pneumonia to prevent misdiagnosis and delays in appropriate management.

Role of ultrasound in the evaluation of first-trimester pregnancies in the acute setting.

In patients presenting for an evaluation of pregnancy in the first trimester, transvaginal ultrasound is the modality of choice for establishing the presence of an intrauterine pregnancy; evaluating pregnancy viability, gestational age, and multiplicity; detecting pregnancy-related complications; and diagnosing ectopic pregnancy. In this pictorial review article, the sonographic appearance of a normal intrauterine gestation and the most common complications of pregnancy in the first trimester in the acute setting are discussed.

Pancreaticobiliary Trauma: A Multimodality Imaging Update.

Pancreaticobiliary injury is an uncommon entity which more often occurs in the setting of blunt than penetrating trauma. We present cases of pancreaticobiliary traumatic injuries from our Level 1 trauma center to illustrate an imaging update on the spectrum of injuries and correlation with current grading systems.

KLF15 is a molecular link between endoplasmic reticulum stress and insulin resistance.

Obesity places major demands on the protein folding capacity of the endoplasmic reticulum (ER), resulting in ER stress, a condition that promotes hepatic insulin resistance and steatosis. Here we identify the transcription factor, Kruppel-like factor 15 (KLF15), as an essential mediator of ER stress-induced insulin resistance in the liver. Mice with a targeted deletion of KLF15 exhibit increased hepatic ER stress, inflammation, and JNK activation compared to WT mice; however, KLF15 (-/-) mice are protected against hepatic insulin resistance and fatty liver under high-fat feeding conditions and in response to pharmacological induction of ER stress.

Pathological endoplasmic reticulum stress mediated by the IRE1 pathway contributes to pre-insulitic beta cell apoptosis in a virus-induced rat model of type 1 diabetes.

Aims/hypothesis: We hypothesised that pathological endoplasmic reticulum (ER) stress contributes to beta cell death during development of type 1 diabetes. In this study, we investigated the occurrence of beta cell ER stress and the signalling pathways involved during discrete stages of autoimmune diabetes progression. The virus-inducible BBDR rat model was used to systematically interrogate the three main ER stress signalling pathways (IRE1 [inositol-requiring protein-1], PERK [double-stranded RNA-dependent protein kinase (PKR)-like ER kinase] and ATF6 [activating transcription factor 6]) in pancreatic beta cells during type 1 diabetes development.

Thioredoxin-interacting protein mediates ER stress-induced β cell death through initiation of the inflammasome.

Recent clinical and experimental evidence suggests that endoplasmic reticulum (ER) stress contributes to the life-and-death decisions of β cells during the progression of type 1 and type 2 diabetes. Although crosstalk between inflammation and ER stress has been suggested to play a significant role in β cell dysfunction and death, a key molecule connecting ER stress to inflammation has not been identified. Here we report that thioredoxin-interacting protein (TXNIP) is a critical signaling node that links ER stress and inflammation.

Cytoplasmic polyadenylation element binding protein deficiency stimulates PTEN and Stat3 mRNA translation and induces hepatic insulin resistance.

The cytoplasmic polyadenylation element binding protein CPEB1 (CPEB) regulates germ cell development, synaptic plasticity, and cellular senescence. A microarray analysis of mRNAs regulated by CPEB unexpectedly showed that several encoded proteins are involved in insulin signaling. An investigation of Cpeb1 knockout mice revealed that the expression of two particular negative regulators of insulin action, PTEN and Stat3, were aberrantly increased.

A novel role for the centrosomal protein, pericentrin, in regulation of insulin secretory vesicle docking in mouse pancreatic beta-cells.

The centrosome is important for microtubule organization and cell cycle progression in animal cells. Recently, mutations in the centrosomal protein, pericentrin, have been linked to human microcephalic osteodysplastic primordial dwarfism (MOPD II), a rare genetic disease characterized by severe growth retardation and early onset of type 2 diabetes among other clinical manifestations. While the link between centrosomal and cell cycle defects may account for growth deficiencies, the mechanism linking pericentrin mutations with dysregulated glucose homeostasis and pre-pubertal onset of diabetes is unknown.

CHOP mediates endoplasmic reticulum stress-induced apoptosis in Gimap5-deficient T cells.

Gimap5 (GTPase of the immunity-associated protein 5) has been linked to the regulation of T cell survival, and polymorphisms in the human GIMAP5 gene associate with autoimmune disorders. The BioBreeding diabetes-prone (BBDP) rat has a mutation in the Gimap5 gene that leads to spontaneous apoptosis of peripheral T cells by an unknown mechanism. Because Gimap5 localizes to the endoplasmic reticulum (ER), we hypothesized that absence of functional Gimap5 protein initiates T cell death through disruptions in ER homeostasis.

Protein kinase C signaling during T cell activation induces the endoplasmic reticulum stress response.

T cell receptor (TCR) ligation (signal one) in the presence of co-stimulation (signal two) results in downstream signals that increase protein production enabling naïve T cells to fully activate and gain effector function. Enhanced production of proteins by a cell requires an increase in endoplasmic reticulum (ER) chaperone expression, which is accomplished through activation of a cellular mechanism known as the ER stress response. The ER stress response is initiated during the cascade of events that occur for the activation of many cells; however, this process has not been comprehensively studied for T cell function.