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.

Spectral molecular imaging is a new imaging technique able to discriminate and quantify different components of tissue simultaneously at high spatial and high energy resolution. Our MARS scanner is an x-ray based small animal CT system designed to be used in the diagnostic energy range (20 -140 keV). In this paper, we demonstrate the use of the MARS scanner, equipped with the Medipix3RX spectroscopic photon-processing detector, to discriminate fat, calcium, and water in tissue. We present data collected from a sample of lamb meat including bone as an illustrative example of human tissue imaging. The data is analyzed using our 3D Algebraic Reconstruction Algorithm (MARS-ART) and by material decomposition based on a constrained linear least squares algorithm. The results presented here clearly show the quantification of lipid-like, water-like and bone-like components of tissue. However, it is also clear to us that better algorithms could extract more information of clinical interest from our data. Because we are one of the first to present data from multi-energy photonprocessing small animal CT systems, we make the raw, partial and fully processed data available with the intention that others can analyze it using their familiar routines. The raw, partially processed and fully processed data of lamb tissue along with the phantom calibration data can be found at [http://hdl.handle.net/10092/8531].

The heart adapts to an increased workload through the activation of a hypertrophic response within the cardiac ventricles. This response is characterized by both an increase in the size of the individual cardiomyocytes and an induction of a panel of genes normally expressed in the embryonic and neonatal ventricle, such as atrial natriuretic peptide (ANP). ANP and brain natriuretic peptide (BNP) exert their biological actions through activation of the natriuretic peptide receptor-1 (Npr1). The current study examined mice lacking Npr1 (Npr1−/−) activity and investigated the effects of the absence of Npr1 signaling during cardiac development on embryo viability, cardiac structure and gene and protein expression. Npr1−/−embryos were collected at embryonic day (ED) 12.5, 15.5 and neonatal day 1 (ND 1). Npr1−/−embryos occurred at the expected Mendelian frequency at ED 12.5, but knockout numbers were significantly decreased at ED 15.5 and ND 1. There was no indication of cardiac structural abnormalities in surviving embryos. However, Npr1−/−embryos exhibited cardiac enlargement (without fibrosis) from ED 15.5 as well as significantly increased ANP mRNA and protein expression compared to wild-type (WT) mice, but no concomitant increase in expression of the hypertrophy-related transcription factors, Mef2A, Mef2C, GATA-4, GATA-6 or serum response factor (SRF). However, there was a significant decrease in Connexin-43 (Cx43) gene and protein expression at mid-gestation in Npr1−/−embryos. Our findings suggest that the mechanism by which natriuretic peptide signaling influences cardiac development in Npr1−/− mice is distinct from that seen during the development of pathological cardiac hypertrophy and fibrosis. The decreased viability of Npr1−/−embryos may result from a combination of cardiomegaly and dysregulated Cx43 protein affecting cardiac contractility.

Spectral computed tomography offers new insights into tissue characterisation. Components of vulnerable atherosclerotic plaque are spectrally distinct with intrinsic contrast. Spectral CT of excised atherosclerotic plaques can display iron, calcium and lipid. Calcium deposits are larger than iron deposits in atheroma. Spectral CT may help in the non-invasive detection of vulnerable plaques.