Use of compressed sensing to reduce scan time and breath-holding for cardiac cine balanced steady-state free precession magnetic resonance imaging in children and young adults.

BACKGROUND: Conventional pediatric volumetric MRI acquisitions of a short-axis stack typically require multiple breath-holds under anesthesia. OBJECTIVE: Here, we aimed to validate a vendor-optimized compressed-sensing approach to reduce scan time during short-axis balanced steady-state free precession (bSSFP) cine imaging. MATERIALS AND METHODS: Imaging was performed in 28 patients (16±9 years) in this study on a commercial 3-tesla (T) scanner using retrospective electrocardiogram-gated cine bSSFP. Cine short-axis images covering both ventricles were acquired with conventional parallel imaging and a vendor-optimized parallel imaging/compressed-sensing approach. Qualitative Likert scoring for blood-myocardial contrast, edge definition, and presence of artifact was performed by two experienced radiologists. Quantitative comparisons were performed including biventricular size and function. A paired t-test was used to detect significant differences (P<0.05). RESULTS: Scan duration was 7±2 s/slice for conventional imaging (147±33 s total) vs. 4±2 s/slice for compressed sensing (83±28 s total). No significant differences were found with qualitative image scores for blood-myocardial contrast, edge definition, and presence of artifact. No significant differences were found in volumetric analysis between the two sequences. The number of breath-holds was 10±4 for conventional imaging and 5±3 for compressed sensing. CONCLUSION: Compressed sensing allowed for a 50% reduction in the number of breath-holds and a 43% reduction in the total scan time without differences in the qualitative or quantitative measurements as compared to the conventional technique.

Cardiac MRI Myocardial Functional and Tissue Characterization Detects Early Cardiac Dysfunction in a Mouse Model of Chemotherapy-Induced Cardiotoxicity.

BACKGROUND: Doxorubicin and doxorubicin-trastuzumab combination chemotherapy have been associated with cardiotoxicity that eventually leads to heart failure and may limit dose-effective cancer treatment. Current diagnostic strategies rely on decreased ejection fraction (EF) to diagnose cardiotoxicity. PURPOSE: The aim of this study is to explore the potential of cardiac MR (CMR) imaging to identify imaging biomarkers in a mouse model of chemotherapy-induced cardiotoxicity. METHODS: A cumulative dose of 25 mg/kg doxorubicin was administered over three weeks using subcutaneous pellets (n = 9, Dox). Another group (n = 9) received same dose of Dox and a total of 10 mg/kg trastuzumab (DT). Mice were imaged at baseline, 5/6 weeks and 10 weeks post-treatment on a 7T MRI system. The protocol included short-axis cine MRI covering the left ventricle (LV) and mid-ventricular short-axis tissue phase mapping (TPM), pre- and post-contrast T1 mapping, T2 mapping and Displacement Encoding with Stimulated Echoes (DENSE) strain encoded MRI. EF, peak myocardial velocities, native T1, T2, extracellular volume (ECV), and myocardial strain were quantified. N = 7 mice were sacrificed for histopathologic assessment of apoptosis at 5/6 weeks. RESULTS: Global peak systolic longitudinal velocity was reduced at 5/6 weeks in Dox (0.6 ± 0.3 vs 0.9 ± 0.3, p = 0.02). In the Dox group, native T1 was reduced at 5/6 weeks (1.3 ± 0.2 ms vs 1.6 ± 0.2 ms, p = 0.02), and relatively normalized at week 10 (1.4 ± 0.1 ms vs 1.6 ± 0.2 ms, p > 0.99). There was no change in EF and other MRI parameters and histopathologic results demonstrated minimal apoptosis in all mice (~1-2 apoptotic cell/high power field), suggesting early-stage cardiotoxicity. CONCLUSIONS: In a mouse model of chemotherapy-induced cardiotoxicity using doxorubicin and trastuzumab, advanced CMR shows promise in identifying treatment-related decrease in myocardial velocity and native T1 prior to the onset of cardiomyocyte apoptosis and reduction of EF.

Rapid dealiasing of undersampled, non-Cartesian cardiac perfusion images using U-net.

Compressed sensing (CS) is a promising method for accelerating cardiac perfusion MRI to achieve clinically acceptable image quality with high spatial resolution (1.6 × 1.6 × 8 mm3 ) and extensive myocardial coverage (6-8 slices per heartbeat). A major disadvantage of CS is its relatively lengthy processing time (~8 min per slice with 64 frames using a graphics processing unit), thereby making it impractical for clinical translation. The purpose of this study was to implement and test whether an image reconstruction pipeline including a neural network is capable of reconstructing 6.4-fold accelerated, non-Cartesian (radial) cardiac perfusion k-space data at least 10 times faster than CS, without significant loss in image quality. We implemented a 3D (2D + time) U-Net and trained it with 132 2D + time datasets (coil combined, zero filled as input; CS reconstruction as reference) with 64 time frames from 28 patients (8448 2D images in total). For testing, we used 56 2D + time coil-combined, zero-filled datasets (3584 2D images in total) from 12 different patients as input to our trained U-Net, and compared the resulting images with CS reconstructed images using quantitative metrics of image quality and visual scores (conspicuity of wall enhancement, noise, artifacts; each score ranging from 1 (worst) to 5 (best), with 3 defined as clinically acceptable) evaluated by readers. Including pre- and post-processing steps, compared with CS, U-Net significantly reduced the reconstruction time by 14.4-fold (32.1 ± 1.4 s for U-Net versus 461.3 ± 16.9 s for CS, p < 0.001), while maintaining high data fidelity (structural similarity index = 0.914 ± 0.023, normalized root mean square error = 1.7 ± 0.3%, identical mean edge sharpness of 1.2 mm). The median visual summed score was not significantly different (p = 0.053) between CS (14; interquartile range (IQR) = 0.5) and U-Net (12; IQR = 0.5). This study shows that the proposed pipeline with a U-Net is capable of reconstructing 6.4-fold accelerated, non-Cartesian cardiac perfusion k-space data 14.4 times faster than CS, without significant loss in data fidelity or image quality.

Slow-Release Doxorubicin Pellets Generate Myocardial Cardiotoxic Changes in Mice Without Significant Systemic Toxicity.

An increasing volume of pre-clinical and clinical-translational research is attempting to identify novel biomarkers for improved diagnosis and risk-stratification of chemotherapy-induced cardiotoxicity. Most published animal models have employed weekly intraperitoneal injections of doxorubicin to reach a desired cumulative dose. This approach can be associated with severe systemic toxicity which limits the animal model usefulness, particularly for advanced imaging. In the current study, slow-release subcutaneous doxorubicin pellets demonstrated histopathologic evidence of cardiotoxicity at doses similar to standard human dose-equivalents without limiting animal survival or ability to participate in advanced imaging studies. This approach may provide a more robust cardiotoxicity animal model.

Comprehensive evaluation of macroscopic and microscopic myocardial fibrosis by cardiac MR: intra-individual comparison of gadobutrol versus gadoterate meglumine.

PURPOSE: Late gadolinium enhancement cardiac MR (LGE-CMR) and extracellular volume fraction (ECV-CMR) are widely used to evaluate macroscopic and microscopic myocardial fibrosis. Macrocyclic contrast media are increasingly used off-label for myocardial scar assessment, given the superior safety profile of these agents. We aimed to assess the performance of two macrocyclic contrast agents, gadoterate meglumine and gadobutrol, for the evaluation of myocardial scar. MATERIAL AND METHODS: Forty subjects (61 ± 11 years, 67.5% men) who underwent LGE-CMR using gadobutrol were prospectively recruited for a research CMR scan using same-dose gadoterate meglumine (0.2 mmol/kg) at 1.5 T. Myocardial scar quantification was performed using a short-axis phase-sensitive inversion recovery (PSIR) Turbo-FLASH and steady-state free precession (SSFP) images. Pre- and post-contrast T1-mapping was employed to assess myocardial ECV. An intraclass correlation coefficient (ICC) was used to check for reliability between the two contrast agents. RESULTS: Using manual thresholding on PSIR Turbo-FLASH images, mean LGE scar percentage (LGE%) was 9.9 ± 9.7% and 9.4 ± 9.7% for gadobutrol and gadoterate meglumine, respectively (p > 0.05) (ICC: 0.99, 95% CI: 0.97-0.99). Using the PSIR SSFP technique and manual thresholding, LGE% averaged 7.5 ± 9.0% and 7.1 ± 8.6% for gadobutrol and gadoterate meglumine, respectively (p > 0.05) (ICC: 0.99, 95% CI: 0.98-0.99). Average ECV with gadobutrol and gadoterate meglumine were similar at 28.40 ± 4.88 and 28.46 ± 4.73 (p > 0.05) with a strong correlation (ICC: 0.98, 95% CI: 0.94-0.99). CONCLUSION: We found LGE- and ECV-CMR values derived from gadoterate meglumine comparable to values derived from gadobutrol. Gadoterate meglumine has a comparable performance to gadobutrol in identifying LGE-derived myocardial scar both qualitatively and quantitatively. KEY POINTS: • Late gadolinium-enhancement cardiac MR (LGE-MR) and extracellular volume (ECV) fraction are widely used to evaluate macroscopic and microscopic myocardial fibrosis. • Macrocyclic contrast media are increasingly used off-label for myocardial scar assessment, given the presumed superior safety profile of these agents. • LGE- and ECV-CMR values derived from gadoterate meglumine are comparable to values derived from gadobutrol.

Accelerated, free-breathing, noncontrast, electrocardiograph-triggered, thoracic MR angiography with stack-of-stars k-space sampling and GRASP reconstruction.

PURPOSE: To develop an accelerated, free-breathing, noncontrast, electrocardiograph-triggered, thoracic MR angiography (NC-MRA) pulse sequence capable of achieving high spatial resolution at clinically acceptable scan time and test whether it produces clinically acceptable image quality in patients with suspected aortic disease. METHODS: We modified a "coronary" MRA pulse sequence to use a stack-of-stars k-space sampling pattern and combined it with golden-angle radial sparse parallel (GRASP reconstruction to enable self-navigation of respiratory motion and high data acceleration. The performance of the proposed NC-MRA was evaluated in 13 patients, where clinical standard contrast-enhanced MRA (CE-MRA) was used as control. For visual analysis, two readers graded the conspicuity of vessel lumen, artifacts, and noise level on a 5-point scale (overall score index = sum of three scores). The aortic diameters were measured at seven standardized locations. The mean visual scores, inter-observer variability, and vessel diameters were compared using appropriate statistical tests. RESULTS: The overall mean visual score index (12.1 ± 1.7 for CE-MRA versus 12.1 ± 1.0 for NC-MRA) scores were not significantly different (P > 0.16). The two readers' scores were significantly different for CE-MRA (P = 0.01) but not for NC-MRA (P = 0.21). The mean vessel diameters were not significantly different, except at the proximal aortic arch (P < 0.03). The mean diameters were strongly correlated (R2 ≥ 0.96) and in good agreement (absolute mean difference ≤ 0.01 cm and 95% confidence interval ≤ 0.62 cm). CONCLUSION: This study shows that the proposed NC-MRA produces clinically acceptable image quality in patients at high spatial resolution (1.5 mm × 1.5 mm × 1.5 mm) and clinically acceptable scan time (~6 min).

Accelerated, first-pass cardiac perfusion pulse sequence with radial k-space sampling, compressed sensing, and k-space weighted image contrast reconstruction tailored for visual analysis and quantification of myocardial blood flow.

PURPOSE: To develop an accelerated cardiac perfusion pulse sequence and test whether it is capable of increasing spatial coverage, generating high-quality images, and enabling quantification of myocardial blood flow (MBF). METHODS: We implemented an accelerated first-pass cardiac perfusion pulse sequence by combining radial k-space sampling, compressed sensing (CS), and k-space weighted image contrast (KWIC) filtering. The proposed and clinical standard pulse sequences were evaluated in a randomized order in 13 patients at rest. For visual analysis, 3 readers graded the conspicuity of wall enhancement, artifact, and noise level on a 5-point Likert scale (overall score index = sum of 3 individual scores). Resting MBF was calculated using a Fermi function model with and without KWIC filtering. Mean visual scores and MBF values were compared between sequences using appropriate statistical tests. RESULTS: The proposed pulse sequence produced greater spatial coverage (6-8 slices) with higher spatial resolution (1.6 × 1.6 × 8 mm3 ) and shorter readout duration (78 ms) compared to clinical standard (3-4 slices, 3 × 3 × 8 mm3 , 128 ms, respectively). The overall image score index between accelerated (11.1 ± 1.3) and clinical standard (11.2 ± 1.3) was not significantly different (P = 0.64). Mean resting MBF values with KWIC filtering (0.9-1.2 mL/g/min across different slices) were significantly lower (P < 0.0001) than those without KWIC filtering (3.1-4.3 mL/g/min) and agreed better with values reported in literature. CONCLUSION: An accelerated, first-pass cardiac perfusion pulse sequence with radial k-space sampling, CS, and KWIC filtering is capable of increasing spatial coverage, generating high-quality images, and enabling quantification of MBF.

Acute CD47 Blockade During Ischemic Myocardial Reperfusion Enhances Phagocytosis-Associated Cardiac Repair.

Our data suggest that, after a myocardial infarction, integrin-associated protein CD47 on cardiac myocytes is elevated. In culture, increased CD47 on the surface of dying cardiomyocytes impairs phagocytic removal by immune cell macrophages. After myocardial ischemia and reperfusion, acute CD47 inhibition with blocking antibodies enhanced dead myocyte clearance by cardiac phagocytes and also improved the resolution of cardiac inflammation, reduced infarct size, and preserved cardiac contractile function. Early targeting of CD47 in the myocardium after reperfusion may be a new strategy to enhance wound repair in the ischemic heart.

Indoor terpene emissions from cooking with herbs and pepper and their secondary organic aerosol production potential.

Cooking is widely recognized as an important source of indoor and outdoor particle and volatile organic compound emissions with potential deleterious effects on human health. Nevertheless, cooking emissions remain poorly characterized. Here the effect of herbs and pepper on cooking emissions was investigated for the first time to the best of our knowledge using state of the art mass spectrometric analysis of particle and gas-phase composition. Further, the secondary organic aerosol production potential of the gas-phase emissions was determined by smog chamber aging experiments. The emissions of frying meat with herbs and pepper include large amounts of mono-, sesqui- and diterpenes as well as various terpenoids and p-cymene. The average total terpene emission rate from the use of herbs and pepper during cooking is estimated to be 46 ± 5 gg-1Herbs min-1. These compounds are highly reactive in the atmosphere and lead to significant amounts of secondary organic aerosol upon aging. In summary we demonstrate that cooking with condiments can constitute an important yet overlooked source of terpenes in indoor air.

Cardiovascular magnetic resonance detects the progression of impaired myocardial perfusion reserve and increased left-ventricular mass in mice fed a high-fat diet.

BACKGROUND: Impaired myocardial perfusion reserve (MPR) is prevalent in obesity and diabetes, even in the absence of obstructive coronary artery disease (CAD), and is prognostic of adverse events. We sought to establish the time course of reduced MPR and to investigate associated vascular and tissue properties in mice fed a high-fat diet (HFD), as they are an emerging model of human obesity, diabetes, and reduced MPR without obstructive CAD. METHODS: C57Bl/6 mice fed a HFD or a low-fat diet (control) were imaged at 6, 12, 18 and 24 weeks post-diet. The cardiovascular magnetic resonance (CMR) protocol included multi-slice cine imaging to assess ejection fraction (EF), left-ventricular (LV) mass, LV wall thickness (LVWT), and LV volumes, and first-pass perfusion CMR to quantify MPR. Coronary vascular reactivity, aortic atherosclerosis, myocardial capillary density and tissue fibrosis were also assessed. RESULTS: Body weight was increased in HFD mice at 6-24 weeks post-diet (p < 0.05 vs. control). MPR in HFD mice was reduced and LV mass and LVWT were increased in HFD mice at 18 and 24 weeks post-diet (p < 0.05 vs. control). Coronary arteriolar vascular reactivity to adenosine and acetylcholine were reduced in HFD mice (p < 0.05 vs. control). There were no significant differences in cardiac volumes, EF, or capillary density measurements between the two groups. Histology showed interstitial fibrosis in HFD and no aortic atherosclerosis in either group. CONCLUSIONS: C57Bl/6 mice fed a HFD for 18-24 weeks have progressively increased LV mass and impaired MPR with fibrosis, normal capillary density and no aortic plaque. These results establish C57Bl/6 mice fed a HFD for 18-24 weeks as a model of impaired MPR without obstructive CAD due to obesity and diabetes.

Characterization of Gas-Phase Organics Using Proton Transfer Reaction Time-of-Flight Mass Spectrometry: Cooking Emissions.

Cooking processes produce gaseous and particle emissions that are potentially deleterious to human health. Using a highly controlled experimental setup involving a proton-transfer-reaction time-of-flight mass spectrometer (PTR-ToF-MS), we investigate the emission factors and the detailed chemical composition of gas phase emissions from a broad variety of cooking styles and techniques. A total of 95 experiments were conducted to characterize nonmethane organic gas (NMOG) emissions from boiling, charbroiling, shallow frying, and deep frying of various vegetables and meats, as well as emissions from vegetable oils heated to different temperatures. Emissions from boiling vegetables are dominated by methanol. Significant amounts of dimethyl sulfide are emitted from cruciferous vegetables. Emissions from shallow frying, deep frying and charbroiling are dominated by aldehydes of differing relative composition depending on the oil used. We show that the emission factors of some aldehydes are particularly large which may result in considerable negative impacts on human health in indoor environments. The suitability of some of the aldehydes as tracers for the identification of cooking emissions in ambient air is discussed.

Repeatability and variability of myocardial perfusion imaging techniques in mice: Comparison of arterial spin labeling and first-pass contrast-enhanced MRI.

PURPOSE: Preclinical imaging of myocardial blood flow (MBF) can elucidate molecular mechanisms underlying cardiovascular disease. We compared the repeatability and variability of two methods, first-pass MRI and arterial spin labeling (ASL), for imaging MBF in mice. METHODS: Quantitative perfusion MRI in mice was performed using both methods at rest, with a vasodilator, and one day after myocardial infarction. Image quality (score of 1-5; 5 best), between-session coefficient of variability (CVbs ), intra-user coefficient of variability (CVintra-user ), and inter-user coefficient of variability (CVinter-user ) were assessed. Acquisition time was 1-2 min for first-pass MRI and approximately 40 min for ASL. RESULTS: Image quality was higher for ASL (3.94 ± 0.09 versus 2.88 ± 0.10; P < 0.05). Infarct zone CVbs was lower with first-pass (17 ± 3% versus 46 ± 9%; P < 0.05). The stress perfusion CVintra-user was lower for ASL (3 ± 1% versus 14 ± 3%; P < 0.05). The stress perfusion CVinter-user was lower for ASL (4 ± 1% versus 17 ± 4%; P < 0.05). CONCLUSION: For low MBF conditions such as infarct, first-pass MRI is preferred due to better repeatability and variability. At high MBF such as at vasodilation, ASL may be more suitable due to superior image quality and lower user variability. First-pass MRI has a substantial speed advantage. Magn Reson Med 75:2394-2405, 2016. © 2015 Wiley Periodicals, Inc.

Glycated serum albumin stimulates expression of endothelial cell specific molecule-1 in human umbilical vein endothelial cells: Implication in diabetes mediated endothelial dysfunction.

Pro-inflammatory conditions induced by products of protein glycation in diabetes substantially enhance the risk of endothelial dysfunction and related vascular complications. Endothelial cell specific molecule-1 (ESM-1) or endocan has been demonstrated as a potential biomarker in cancer and sepsis. Its role in diabetes-induced pathologies remains unknown. The expression of ESM-1 gene is under cytokine regulation, indicating its role in endothelium-dependent pathological disorders. In this study, we investigated the effect of advanced glycated human serum albumin (AGE-HSA) on the production of ESM-1. We show that AGE-HSA exerts a modulating role on the expression of ESM-1 in human umbilical vein endothelial cells. It up-regulates expression of ESM-1 protein in a dose-dependent manner which correlates with its messenger RNA (mRNA) transcription. RAGE and galectin-3, both AGE receptors, show antagonistic action on its expression. While gene silencing of RAGE has down-regulatory effect, that of galectin-3 has up-regulatory effect on AGE-induced expression of ESM-1. Inhibition of MAPKKK and JNK pathways did not alter the expression. In contrast, phosphatidylinositol 3 kinase (PI3K) inhibition significantly up-regulated ESM-1 expression. In conclusion, these results suggest that AGE-induced activation of human umbilical vein endothelial cells promotes formation of endocan which is an endothelial dysfunction marker and may be related to vascular disease in diabetes.

A novel cardiac muscle-derived biomaterial reduces dyskinesia and postinfarct left ventricular remodeling in a mouse model of myocardial infarction.

Extracellular matrix (ECM) degradation after myocardial infarction (MI) leaves the myocardium structurally weakened and, as a result, susceptible to early infarct zone dyskinesia and left ventricular (LV) remodeling. While various cellular and biomaterial preparations have been transplanted into the infarct zone in hopes of improving post-MI LV remodeling, an allogeneic cardiac muscle-derived ECM extract has yet to be developed and tested in the setting of reperfused MI. We sought to determine the effects of injecting a novel cardiac muscle-derived ECM into the infarct zone on early dyskinesia and LV remodeling in a mouse model of MI. Cardiac muscle ECM was extracted from frozen mouse heart tissue by a protocol that enriches for basement membrane constituents. The extract was injected into the infarct zone immediately after ischemia/reperfusion injury (n = 6). Echocardiography was performed at baseline and at days 2, 7, 14, and 28 post-MI to assess 3D LV volumes and cardiac function, as compared to infarcted controls (n = 9). Early infarct zone dyskinesia was measured on day 2 post-MI using a novel metric, the dyskinesia index. End-systolic volume was significantly reduced in the ECM-treated group compared to controls by day 14. Ejection fraction and stroke volume were also significantly improved in the ECM-treated group. ECM-treated hearts showed a significant (P < 0.005) reduction in dyskinetic motion on day 2. Thus, using high-frequency ultrasound, it was shown that treatment with a cardiac-derived ECM preparation reduced early infarct zone dyskinesia and post-MI LV remodeling in a mouse model of reperfused MI.

Is It Safe to Provide Abortion Pills over the Counter? A Study on Outcome Following Self-Medication with Abortion Pills.

BACKGROUND: Medical abortion is a safe method of termination of pregnancy when performed as per guidelines with a success rate of 92-97 %. But self-administration of abortion pills is rampant throughout the country due to over the counter availability of these drugs and complications are not uncommon due to this practice. The society perceives unsupervised medical abortion as a very safe method of termination and women use this as a method of spacing. AIM OF THE STUDY: The aim of this study was to study the implications of self-administration of abortion pills by pregnant women. MATERIALS AND METHODS: Retrospective observational study done in Sri Manakula Vinayagar Medical College & Hospital between the period of July 2013 to June2014. Case sheets were analysed to obtain data regarding self-administration of abortion pills and complications secondary to its administration. The following data were collected. Age, marital status, parity, duration of pregnancy as perceived by the women, confirmation of pregnancy, duration between pill intake and visit to hospital, whether any intervention done elsewhere, any known medical or surgical complications, Hb level on admission, whether patient was in shock, USG findings, evidence of sepsis, blood transfusion, treatment given and duration of hospital stay. Descriptive analysis of the collected data was done. RESULTS: Among the 128 cases of abortion in the study period, 40 (31.25%) patients had self-administered abortion pills. Among these 40 patients 27.5% had consumed abortion pills after the approved time period of 63 days of which 17.5% had consumed pills after 12 weeks of gestation. The most common presentation was excessive bleeding (77.5%) Severe anaemia was found in 12.5% of the patients and 5% of patients presented with shock. The outcome was as follows : 62.5% of the patients were found to have incomplete abortion, 22.5% had failed abortion and 7.5% of patients had incomplete abortion with sepsis. Surgical evacuation was performed in 67.5% of the patients whereas 12.5% of the patients required surgical evacuation with blood transfusion. Medical methods were used in 15% of the patients whereas 2.5% required transfusion along with medical methods. CONCLUSION: Unsupervised medical abortion can lead to increased maternal morbidity and mortality. To curtail this harmful practice, strict legislations are required to monitor and also to restrict the sales of abortion pills over the counter and access to abortion pills for the public should be only through centers approved for MTP. Large scale prospective studies are required to assess the actual magnitude of this problem.

Accelerated dual-contrast first-pass perfusion MRI of the mouse heart: development and application to diet-induced obese mice.

PURPOSE: Gene-modified mice may be used to elucidate molecular mechanisms underlying abnormal myocardial blow flow (MBF). We sought to develop a quantitative myocardial perfusion imaging technique for mice and to test the hypothesis that myocardial perfusion reserve (MPR) is reduced in a mouse model of diet-induced obesity (DIO). METHODS: A dual-contrast saturation-recovery sequence with ky -t undersampling and a motion-compensated compressed sensing reconstruction algorithm was developed for first-pass MRI on a small-bore 7 Tesla system. Control mice were imaged at rest and with the vasodilators ATL313 and Regadenoson (n = 6 each). In addition, we imaged mice fed a high-fat diet (HFD) for 24 weeks. RESULTS: In control mice, MBF was 5.7 ± 0.8 mL/g/min at rest and it increased to 11.8 ± 0.6 mL/g/min with ATL313 and to 10.4 ± 0.3 mL/g/min with Regadenoson. In HFD mice, we detected normal resting MBF (5.6 ± 0.4 versus 5.0 ± 0.3 on control diet), low MBF at stress (7.7 ± 0.4 versus 10.4 ± 0.3 on control diet, P < 0.05), and reduced MPR (1.4 ± 0.2 versus 2.0 ± 0.3 on control diet, P < 0.05). CONCLUSION: Accelerated dual-contrast first-pass MRI with motion-compensated compressed sensing provides spatiotemporal resolution suitable for measuring MBF in free-breathing mice, and detected reduced MPR in DIO mice. These techniques may be used to study molecular mechanisms that underlie abnormal myocardial perfusion.

Should clinical trial research of psychotropic medication in autism control for gastrointestinal symptoms?

Recent research has established that many children and adult diagnosed with autism experience gastrointestinal symptoms. Furthermore, research has demonstrated that gastrointestinal symptoms can impact drug availability and absorption. In this paper we explore the presence of gastrointestinal symptoms in autism and put forth a call for a formal evaluation of the potential relationship between gastrointestinal symptoms and psychotropic medication effectiveness in individuals with autism.

Chromatin condensation dynamics and implications of induced premature chromosome condensation.

Somatic cell cycle is a dynamic process with sequential events that culminate in cell division. Several physiological activities occur in the cytoplasm and nucleus during each of the cell cycle phases which help in doubling of genetic content, organized arrangement of the duplicated genetic material and perfect mechanism for its equal distribution to the two daughter cells formed. Also, the cell cycle checkpoints ensure that the genetic material is devoid of damages thus ensuring unaltered transmission of genetic information. Two important phenomena occurring during the cell cycle are the DNA condensation and decondensation cycles in the nucleus along with the cyclic expression and functioning of certain specific proteins that help in the same. Several protein families including Cyclins, cyclin dependent kinases, condensins, cohesins and surivins ensure error free, stage specific DNA condensation and decondensation by their highly specific, controlled orchestrated presence and action. Understanding the molecular mechanisms of chromatin compaction towards formation of the structural units, the chromosomes, give us valuable insights into the cellular physiology and also direct us to techniques such as premature chromosome condensation. The techniques of inducing 'prophasing' of interphase cells are undergoing rapid advances which have multidimensional applications for basic research and direct applications.

Monocyte and/or macrophage infiltration of heart after myocardial infarction: MR imaging by using T1-shortening liposomes.

PURPOSE: To test the hypothesis that magnetic resonance (MR) imaging R1 (R1 = 1/T1) mapping after selectively labeling monocytes with a T1-shortening contrast agent in vivo would enable the quantitative measurement of their spatiotemporal kinetics in the setting of infarct healing. MATERIALS AND METHODS: All procedures were performed in mice and were approved by the institutional committee on animal research. One hundred microliters of dual-labeled liposomes (DLLs) containing gadolinium (Gd)-diethylenetriaminepentaacetic acid (DTPA)-bis(stearylamide) and DiI dye were used to label monocytes 2 days before myocardial infarction (MI). MI was induced by occlusion of the left anterior descending coronary artery for 1 hour, followed by reperfusion. MR imaging R1 mapping of mouse hearts was performed at baseline on day -3, on day 0 before MI, and on days 1, 4, and 7 after MI. Mice without labeling were used as controls. ΔR1 was calculated as the difference in R1 between mice with labeling and those without labeling. CD68 immunohistochemistry and DiI fluorescence microscopy were used to confirm that labeled monocytes and/or macrophages infiltrated the postinfarct myocardium. Statistical analysis was performed by using two-way analysis of variance and the unpaired two-sample t test. RESULTS: Infarct zone ΔR1 was slightly but nonsignificantly increased on day 1, maximum on day 4 (P < .05 vs all other days), and started to decrease by day 7 (P < .05 vs days -3, 0, and 1) after MI, closely reflecting the time course of monocyte and/or macrophage infiltration of the infarcted myocardium shown by prior histologic studies. Histologic results confirmed the presence and location of DLL-labeled monocytes and/or macrophages in the infarct zone on day 4 after MI. CONCLUSION: R1 mapping after labeling monocytes with T1-shortening DLLs enables the measurement of post-MI monocyte and/or macrophage spatiotemporal kinetics.