Objectives To determine whether cardiac magnetic resonance (CMR) in vivo T1-mapping can measure myocardial area at risk (AAR) compared with microspheres or T2-mapping CMR. Background If T2-weighted CMR is abnormal in the AAR due to edema related to myocardial ischemia, then T1-weighted CMR should also be able to detect and accurately quantify AAR. Methods Dogs (n=9) underwent a 2 hour coronary occlusion followed by 4 hours of reperfusion. CMR of the left ventricle was performed for mapping of T1 and T2 prior to any contrast administration. AAR was defined as regions which had a T1 or T2 value (ms) greater than 2SD from remote, and regions with microsphere blood flow (ml/min/g) during occlusion less than 2SD from remote. Infarct size was determined by triphenyltetrazolium chloride staining. Results The relaxation parameters T1 and T2 were increased in the AAR compared to remote myocardium (T1: 1133±55 vs. 915±33ms, T2: 71±6 vs. 49±3 ms; mean±SD). On a slice-by-slice basis (n=78 slices), AAR by T1- and T2-mapping correlated (R2=0.95, p<0.001) with good agreement (0.4±16.6 % of slice, mean±2SD). On a whole-heart analysis, T1 measurements of left ventricular mass, AAR and myocardial salvage correlated to microsphere measures (R2=0.94) with good agreement (−1.4±11.2 g of myocardium; mean±2SD). Corresponding T2 measurements of left ventricular mass, AAR, and salvage correlated to microsphere analysis (R2=0.96, agreement 1.6±9.2 g of myocardium; mean±2SD). Median infarct size was 30% of the AAR (range 12–52). Conclusions For determining area at risk after acute myocardial infarction, non-contrast T1-mapping and T2-mapping sequences yield similar quantitative results, and both agree well with microspheres. The relaxation properties T1 and T2 both change in a way that is consistent with the presence of myocardial edema following myocardial ischemia/reperfusion.

SummaryAnthracycline antibiotics have saved the lives of many cancer victims in the 50 plus years since their discovery. A major limitation of their use is the dose-limiting cardiotoxicity. Efforts focusing on understanding the biochemical basis for anthracycline cardiac effects have provided several strategies currently in clinical use: limit dose exposure; encapsulate anthracyclines in liposomes to reduce myocardial uptake; administer concurrently with the iron chelator dexrazoxane to reduce free ironcatalyzed reactive oxygen species formation; modification of anthracycline structure in an effort to reduce myocardial toxicity. In spite of these efforts, anthracycline-induced heart failure continues to occur with consequences for both morbidity and mortality. Our inability to predict and prevent anthracycline cardiotoxicity is in part due to the fact that the molecular and cellular mechanisms remain controversial and incompletely understood. Studies examining the effects of anthracyclines in cardiac myocytes in vitro and small animals in vivo have demonstrated several forms of cardiac injury, and it remains unclear how these translate to the clinical setting. Given the clinical evidence that myocyte death occurs after anthracycline exposure in the form of elevations in serum troponin, myocyte cell death appears to be a probable mechanism for anthracycline-induced cardiac injury. Other mechanisms of myocyte injury include the development of cellular 'sarcopenia' characterized by disruption of normal sarcomere structure. Anthracyclines suppress expression of several cardiac transcription factors, and this may play a role in the development of myocyte death as well as sarcopenia. Degradation of the giant myofilament protein titin may represent an important proximal step that leads to accelerated myofilament degradation. An interesting interaction has been noted clinically between anthracyclines and newer cancer therapies that target the erbB2 receptor tyrosine kinase. There is now evidence that erbB2 signaling in response to the ligand neuregulin regulates anthracycline uptake into cells via the multidrug-resistance protein. Therefore upregulation of cardiac neuregulin signaling may be one strategy to limit myocardial anthracycline injury. Moreover, assessing an individual's risk for anthracycline injury may be improved by having some measure of endogenous activity of this and other myocardial protective signals. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1]): 1) inhibition of both DNA replication and RNA transcription; 2) free radical generation, leading to DNA damag...

a) (b)(c) (d) Figure 1: (a) Conventional photograph of a scene, illuminated by a projector with all its pixels turned on. (b) After measuring the light transport between the projector and the camera using structured illumination, our technique is able to synthesize a photorealistic image from the point of view of the projector. This image has the resolution of the projector and is illuminated by a light source at the position of the camera. The technique can capture subtle illumination effects such as caustics and self-shadowing. Note, for example, how the glass bottle in the primal image (a) appears as the caustic in the dual image (b) and vice-versa. Because we have determined the complete light transport between the projector and camera, it is easy to relight the dual image using a synthetic light source (c) or a light modified by a matte captured later by the same camera (d). AbstractWe present a novel photographic technique called dual photography, which exploits Helmholtz reciprocity to interchange the lights and cameras in a scene. With a video projector providing structured illumination, reciprocity permits us to generate pictures from the viewpoint of the projector, even though no camera was present at that location. The technique is completely image-based, requiring no knowledge of scene geometry or surface properties, and by its nature automatically includes all transport paths, including shadows, inter-reflections and caustics. In its simplest form, the technique can be used to take photographs without a camera; we demonstrate this by capturing a photograph using a projector and a photo-resistor. If the photo-resistor is replaced by a camera, we can produce a 4D dataset that allows for relighting with 2D incident illumination. Using an array of cameras we can produce a 6D slice of the 8D reflectance field that allows for relighting with arbitrary light fields. Since an array of cameras can operate in parallel without interference, whereas an array of light sources cannot, dual photography is fundamentally a more efficient way to capture such a 6D dataset than a system based on multiple projectors and one camera. As an example, we show how dual photography can be used to capture and relight scenes.

Background Chronic methamphetamine (METH) exposure causes neuroadaptations at glutamatergic synapses. Methods To identify the METH-induced epigenetic underpinnings of these adaptations in the brain, we injected increasing METH doses to rats for two weeks and measured striatal glutamate receptor expression. We then quantified the effects of METH exposure on histone acetylation using chromatin immunoprecipitation (ChIP) and qPCR. We also measured METH-induced changes in DNA methylation and hydroxylation by using methylated (Me) and hydroxymethylated (hMe) DNA precipitation (DIP) and qPCR. Results Chronic METH decreased transcript and protein expression of GluA1 and GluA2 AMPAR and GluN1 NMDAR subunits. These changes were associated with decreased electrophysiological glutamatergic responses in striatal neurons. ChIP-PCR revealed that METH decreased enrichment of acetylated histone H4 on GluA1, GluA2, and GluN1 promoters. METH also increased protein levels of histone deacetylases (HDAC1, HDAC2 and SIRT2), protein repressors (REST and CoREST), and of the methylated DNA binding protein, MeCP2. Moreover, METH exposure increased CoREST, MeCP2, and HDAC2, but not SIRT1 or SIRT2, enrichment onto GluA1 and GluA2 gene sequences. Furthermore, METH caused interactions of CoREST and MeCP2 with HDAC2 and of REST with HDAC1. Surprisingly, MeDIP and hMeDIP-PCR revealed METH-induced decreased enrichment of 5-methylcytosine and 5-hydroxymethylcytosine at GluA1 and GluA2 promoter sequences. Furthermore, the HDAC inhibitor, valproic acid, blocked METH-induced decreased expression of AMPAR and NMDAR subunits. Finally, valproic acid also attenuated METH-induced decreased H4K16Ac recruitment on AMPAR gene sequences. Conclusions These observations suggest that histone H4 hypoacetylation might be the main determinant of METH-induced decreased striatal glutamate receptor expression.