Spectral CT distinguishes contrast agents with K-edges only 4 keV apart. Multi-contrast imaging and molecular CT are potential future applications.

The natriuretic peptides, atrial (ANP) and brain natriuretic peptide (BNP) are known to suppress cardiac hypertrophy and fibrosis. Both ANP and BNP exert their bioactivities through the Npr1 receptor, and Npr1 knockout mice (Npr1K/K) exhibit marked cardiac hypertrophy and fibrosis. In this study, we investigated which genes within the hypertrophic and fibrotic pathways are influenced by the lack of Npr1 signalling. cDNA microarray and quantitative real-time PCR (RT-PCR) analyses were performed on cardiac ventricles from Npr1K/K mice. Gene expression at early and late stages during development of hypertrophy was investigated in male and female Npr1K/K mice at 8 weeks and 6 months of age. Heart weight to body weight ratios (HW:BW) were maximally increased in 8-week males (P!0 . 01), whilst HW:BW in females continued to increase progressively up to 6 months (P!0 . 01). This was despite blood pressure being similarly elevated at both the ages in male and female knockout when compared with wild-type (WT) mice (P!0 . 001). Microarray analysis identified altered gene expression at the earliest steps in the hypertrophy-signalling cascade in Npr1K/K mice, particularly calcium-calmodulin signalling and ion channels, with subsequent changes in the expression of intracellular messengers including protein kinases and transcription factors. Real-time PCR analysis confirmed significant differences in gene expression of ANP, BNP, calmodulin 1, histone deacetylase 7a (HDAC7a), protein kinase C (PKC)i, (GATA) 4, collagen 1, phospholamban and transforming growth factor-b1 in Npr1K/K mice when compared with WT (P!0 . 05). The present study implicates the calmodulin-CaMK-Hdac-Mef2 and PKC-MAPK-GATA4 pathways in Npr1 mediation of cardiac hypertrophy.

Spectral CT, using the Medipix3 detector and silicon sensor layer, can quantify certain sets of up to three materials using the proposed method of constrained least squares. The system has some ability to independently distinguish calcium, fat, and water, and these have been quantified within phantom equivalents of fatty liver and atheroma. In this configuration, spectral CT cannot distinguish iron from calcium within soft tissues.

After myocardial infarction (MI), the heart may undergo progressive ventricular remodeling, resulting in a deterioration of cardiac function. TGF-beta is a key cytokine that both initiates and terminates tissue repair, and its sustained production underlies the development of tissue fibrosis, particularly after MI. We investigated the effects of a novel orally active specific inhibitor of the TGF-beta receptor 1 (SD-208) in an experimental model of MI. Mice underwent ligation of the left coronary artery to induce MI and were subsequently treated for 30 d after infarction with either SD-208 or a vehicle control. Blockade of TGF-beta signaling reduced mean arterial pressure in all groups. SD-208 treatment after MI resulted in a trend for reduced ventricular and renal gene expression of TGF-beta-activated kinase-1 (a downstream modulator of TGF-beta signaling) and a significant decrease in collagen 1, in association with a marked decrease in cardiac mass. Post-MI SD-208 treatment significantly reduced circulating levels of plasma renin activity as well as down-regulating the components of the cardiac and renal renin-angiotensin system (angiotensinogen, angiotensin converting enzyme, and angiotensin II type I receptor). Our findings indicate that blockade of the TGF-beta signaling pathway results in significant amelioration of deleterious cardiac remodeling after infarction.

Energy resolving capabilities of X-ray detectors like the Medipix2 and the upcoming Medipix3 offer access to spectral information which is a new domain of information in medical imaging.In conventional CT of a composite object only the cumulative contribution of all involved materials to the attenuation is measurable, but not how much each material component contributes to this attenuation. Therefore, contrast agent can not be distinguished from bone or calcifications. The method of material reconstruction exploits the energy information to determine the partial densities of the involved materials using a Maximum Likelihood approach, i.e. it allows the separation of contrast agent from tissue, bones and calcifications.We have employed the MARS scanner equipped with a Medipix2 MXR and performed a CT scan of a mouse with iodine contrast agent in stomach and bowel. The method allows to separate the iodine contrast agent from all the other absorbing structures. In the iodine image, only the iodine concentration is visible, while the non-iodine (water) image shows all the other tissue structures and bones. The method of material reconstruction was applied to real CT data of a biological sample for the first time.