Cardiac diffusion-weighted and tensor imaging: a Society for Cardiovascular Magnetic Resonance (SCMR) special interest group consensus statement.

Thanks to recent developments in Cardiovascular magnetic resonance (CMR), cardiac diffusion-weighted magnetic resonance is fast emerging in a range of clinical applications. Cardiac diffusion-weighted imaging (cDWI) and diffusion tensor imaging (cDTI) now enable investigators and clinicians to assess and quantify the 3D microstructure of the heart. Free-contrast DWI is uniquely sensitized to the presence and displacement of water molecules within the myocardial tissue, including the intra-cellular, extra-cellular and intra-vascular spaces. CMR can determine changes in microstructure by quantifying: a) mean diffusivity (MD) -measuring the magnitude of diffusion; b) fractional anisotropy (FA) - specifying the directionality of diffusion; c) helix angle (HA) and transverse angle (TA) -indicating the orientation of the cardiomyocytes; d) E2A and E2A mobility - measuring the alignment and systolic-diastolic mobility of the sheetlets, respectively. This document provides recommendations for both clinical and research cDWI and cDTI, based on published evidence when available and expert consensus when not. It introduces the cardiac microstructure focusing on the cardiomyocytes and their role in cardiac physiology and pathophysiology. It highlights methods, observations and recommendations in terminology, acquisition schemes, post-processing pipelines, data analysis and interpretation of the different biomarkers. Despite the ongoing challenges discussed in the document and the need for ongoing technical improvements, it is clear that cDTI is indeed feasible, can be accurately and reproducibly performed and, most importantly, can provide unique insights into myocardial pathophysiology.

VueBox® for quantitative analysis of contrast-enhanced ultrasound in liver tumors1.

Dynamic contrast-enhanced ultrasound (DCE-US) enables quantification of tumor perfusion. VueBox is a platform independent external software using DICOM cine loops which objectively provides various DCE-US parameters of tumor vascularity. This review summaries its use for diagnosis and treatment monitoring of liver tumors. The existing literature provides evidence on the successful application of Vuebox based DCE-US for characterization and differential diagnosis of focal liver lesions, as well as on its use for monitoring of local ablative therapies and of modern systemic treatment in oncology.

Skeletal Effects of Levothyroxine for Subclinical Hypothyroidism in Older Adults: A TRUST Randomized Trial Nested Study.

CONTEXT: Both thyroid dysfunction and levothyroxine (LT4) therapy have been associated with bone loss, but studies on the effect of LT4 for subclinical hypothyroidism (SHypo) on bone yielded conflicting results. OBJECTIVE: To assess the effect of LT4 treatment on bone mineral density (BMD), Trabecular Bone Score (TBS), and bone turnover markers (BTMs) in older adults with SHypo. DESIGN AND INTERVENTION: Planned nested substudy of the double-blind placebo-controlled TRUST trial. Participants with SHypo were randomized to LT4 with dose titration versus placebo with computerized mock titration. SETTING AND PARTICIPANTS: 196 community-dwelling adults over 65 years enrolled at the Swiss TRUST sites had baseline and 1-year follow-up bone examinations; 4 participants withdrew due to adverse events not related to treatment. MAIN OUTCOME MEASURES: One-year percentage changes of BMD, TBS, and 2 serum BTMs (serum CTX-1 [sCTX] and procollagen type 1 N-terminal polypeptide [P1NP]). Student's t-test for unadjusted analyses and linear regression adjusted for clinical center and sex were performed. RESULTS: Mean age was 74.3 years ± 5.7, 45.4% were women, and 19.6% were osteoporotic. The unadjusted 1-year change in lumbar spine BMD was similar between LT4 (+0.8%) and placebo-treated groups (-0.6%; between-groups difference +1.4%: 95% confidence interval [CI] -0.1 to 2.9, P = .059). Likewise, there were no between-group differences in 1-year change in TBS (-1.3%: 95% CI -3.1 to 0.6, P = .19), total hip BMD (-0.2%: 95% CI -1.1 to 0.1, P = .61), or BTMs levels (sCTX +24.1%: 95% CI -7.9 to 56.2, P = .14), or after adjustment for clinical centers and sex. CONCLUSIONS: Over 1-year levothyroxine had no effect on bone health in older adults with SHypo. REGISTRATION: ClinicalTrial.gov NCT01660126 and NCT02491008.

Presentation and outcome of frequent and rare sarcoma histologic subtypes: A study of 10,262 patients with localized visceral/soft tissue sarcoma managed in reference centers.

BACKGROUND: The objective of this study was to describe characteristics at diagnosis and outcomes of adults with soft tissue sarcoma. METHODS: The authors conducted a retrospective multicenter study of 12,262 patients who were treated between January 1980 and 31 December 2013 in French Sarcoma Group centers and enrolled in the "Conticabase." Diagnoses were systematically reviewed by expert pathologists, and entities were classified according to the 2013 World Health Organization classification. Diagnostic characteristics, treatments, and outcomes are described for the entire cohort, for the subgroup of patients with translocation-related sarcomas, and for 9 different histologic subtypes. RESULTS: The results stressed the magnitude of heterogeneity among adult sarcomas. For example, compared with other sarcomas, translocation-related sarcomas (2143 tumors; 20.8%) were associated with a younger age at presentation (40.6 vs 60.0 years; P < .0001), a low rate of predisposing conditions (0.01% vs 22.3%; P < .0001), a higher rate of lymph node involvement (4.7% vs 1.3%; P < .0001), and a higher rate of synchronous metastasis (11.9% vs 6.7%; P < .001); and complete (R0) resection (41.6% vs 31.9%; P < .0001), receipt of (neo)adjuvant radiation therapy (62.6% vs 42.2%; P < .0001), and receipt of (neo)adjuvant chemotherapy (36.6% vs 22.3%; P < .0001) were significantly more frequent. Overall, translocation-related sarcomas were associated with a lower rate of local relapse (18.1% vs 26.0%; P < .0001) but a higher rate of metastatic relapse (42.0% vs 30.7%; P < .0001). CONCLUSIONS: Collaborative efforts are urgently needed to better assess the natural history and management options for every histologic subtype of sarcoma. Cancer 2018;124:1179-87. © 2017 American Cancer Society.

Gluing the 'unwettable': soil-dwelling harvestmen use viscoelastic fluids for capturing springtails.

Gluing can be a highly efficient mechanism of prey capture, as it should require less complex sensory-muscular feedback. Whereas it is well known in insects, this mechanism is much less studied in arachnids, except spiders. Soil-dwelling harvestmen (Opiliones, Nemastomatidae) bear drumstick-like glandular hairs (clavate setae) at their pedipalps, which were previously hypothesized to be sticky and used in prey capture. However, clear evidence for this was lacking to date. Using high-speed videography, we found that the harvestman Mitostoma chrysomelas was able to capture fast-moving springtails (Collembola) just by a slight touch of the pedipalp. Adhesion of single clavate setae increased proportionally with pull-off velocity, from 1 µN at 1 µm s(-1) up to 7 µN at 1 mm s(-1), which corresponds to the typical weight of springtails. Stretched glue droplets exhibited characteristics of a viscoelastic fluid forming beads-on-a-string morphology over time, similar to spider capture threads and the sticky tentacles of carnivorous plants. These analogies indicate that viscoelasticity is a highly efficient mechanism for prey capture, as it holds stronger the faster the struggling prey moves. Cryo-scanning electron microscopy of snap-frozen harvestmen with glued springtails revealed that the gluey secretions have a high affinity to wet the microstructured cuticle of collembolans, which was previously reported to be barely wettable for both polar and non-polar liquids. Glue droplets can be contaminated with the detached scaly setae of collembolans, which may represent a counter-adaptation against entrapment by the glue, similar to the scaly surfaces of Lepidoptera and Trichoptera (Insecta) facilitating escape from spider webs.

Asymptomatic Plasmodium falciparum infection is associated with anaemia in pregnancy and can be more cost-effectively detected by rapid diagnostic test than by microscopy in Kinshasa, Democratic Republic of the Congo.

BACKGROUND: In areas of high malaria transmission, Plasmodium falciparum infection during pregnancy is characterized by malaria-related anaemia, placental malaria and does not always result in clinical symptoms. This situation is associated with poor pregnancy outcomes. The aim of this study was to determine the extent of asymptomatic P. falciparum infection, its relation with anaemia as well as the most cost-effective technique for its diagnosis in healthy pregnant women living in Kinshasa, Democratic Republic of the Congo. METHODS: In a cross-sectional study design, information on socio-demographic characteristics and cost data were collected in healthy pregnant women attending antenatal care consultations. Plasmodium falciparum infection was diagnosed using rapid diagnostic test (RDT), microscopy and polymerase chain reaction (PCR). Haemoglobin concentration was also determined. RESULTS: In total, 332 pregnant women were enrolled. RDT and microscopy data were available for all the blood samples and 166 samples were analysed by PCR. The prevalence of asymptomatic P. falciparum infection using microscopy, RDTs and PCR, were respectively 21.6%, 27.4% and 29.5%. Taking PCR as a reference, RDTs had a sensitivity of 81.6% and a specificity of 94.9% to diagnose asymptomatic P. falciparum infection. The corresponding values for microscopy were 67.3% and 97.4%. The prevalence of anaemia was 61.1% and asymptomatic malaria increased five times the odds (p < 0.001) of having anaemia. RDTs were more cost-effective compared to microscopy. Incremental cost-effectiveness ratio was US$ 63.47 per microscopy adequately diagnosed case. CONCLUSION: These alarming results emphasize the need to actively diagnose and treat asymptomatic malaria infection during all antenatal care visits. Moreover, in DRC, malaria and anaemia control efforts should be strengthened by promoting the use of insecticide-treated nets, intermittent preventive treatment with sulphadoxine-pyrimethamine and iron and folic acid supplements.

Molecular phylogeny of the spider family Sparassidae with focus on the genus Eusparassus and notes on the RTA-clade and 'Laterigradae'.

The phylogeny of the spider family Sparassidae is comprehensively investigated using four molecular markers (mitochondrial COI and 16S; nuclear H3 and 28S). Sparassidae was recovered as monophyletic and as most basal group within the RTA-clade. The higher-level clade Dionycha was not but monophyly of RTA-clade was supported. No affiliation of Sparassidae to other members of the 'Laterigradae' (Philodromidae, Selenopidae and Thomisidae) was observed, and the crab-like posture of this group assumed a result of convergent evolution. Only Philodromidae and Selenopidae were found members of a supported clade, but together with Salticidae and Corinnidae, while Thomisidae was nested within the higher Lycosoidea. Within Sparassidae monophyly of the subfamilies Heteropodinae sensu stricto, Palystinae and Deleninae was recovered. Sparianthinae was supported as the most basal clade within Sparassidae. Sparassinae and the genus Olios were found each to be polyphyletic. Eusparassinae was not recovered monophyletic, with the two original genera Eusparassus and Pseudomicrommata in separate clades and only the latter clustered with most other assumed Eusparassinae, here termed the "African clade". Further focus was on the monophyletic genus Eusparassus and its proposed species groups, of which the dufouri-, walckenaeri- and doriae-group were confirmed as monophyletic with the two latter groups more closely related. According to molecular clock analyses, the divergence time of Sparassidae and Eusparassus was estimated with 186 and 70 million years ago respectively.

A taxonomic catalogue of the Dyspnoi Hansen and Sørensen, 1904 (Arachnida: Opiliones).

An update of the systematics and determination key of the Opiliones suborder Dyspnoi is provided. The included catalogue represents the first comprehensive species and synonymy listing since Roewer (1923). It summarises all taxonomic changes to date and attempts to be a sound basis against the exponential growing number of online errors, for which examples are given. Species taxonomy features most obvious changes within the Nemastomatidae. The number of species in the collective genus Nemastoma is reduced from 96 (Hallan 2005) to its sensu stricto definition of 7, and the excluded names are transferred to other genera or considered as nomina dubia, predominantly in Paranemastoma. The systematics of the superfamily Ischyropsalidoidea is discussed and family-level diagnoses are renewed to support taxonomical changes: The morphological heterogeneity in the Sabaconidae is resolved by reverting the family to its original monogeneric state. Taracus and Hesperonemastoma are separated as Taracidae fam. n., and Crosbycus is tentatively transferred to this assembly. The remaining genera of Ceratolasmatidae, Acuclavella and Ceratolasma, are included as subfamily Ceratolasmatinae in the Ischyropsalididae and Ischyropsalis is assigned subfamily status, respectively. Other nomenclatural acts are restricted to species-group level with the following synonymies established: Sabacon jonesi Goodnight & Goodnight, 1942 syn. n. (=cavicolens (Packard, 1884)), Dicranolasma diomedeum Kulczynski, 1907 syn. n. (=hirtum Loman, 1894), Mitostoma (Mitostoma) sketi Hadzi, 1973a syn. n. (=chrysomelas (Hermann, 1804)), Mitostoma asturicum Roewer, 1951 syn. n. (=pyrenaeum (Simon, 1879a)), Nemastoma formosum Roewer, 1951 syn. n. (=Nemastomella bacillifera bacillifera (Simon, 1879a)), Nemastoma reimoseri Roewer, 1951 syn. n. (=Paranemastoma bicuspidatum (C.L. Koch, 1835)), Nemastoma tunetanum Roewer, 1951 syn. n. (=Paranemastoma bureschi (Roewer, 1926)), Phalangium flavimanum C.L. Koch, 1835 syn. n. (=Paranemastoma quadripunctatum (Perty, 1833)), Crosbycus graecus Giltay, 1932 syn. n. (=Paranemastoma simplex (Giltay, 1932)), Nemastoma bimaculosum Roewer 1951 syn. n. (=Paranemastoma titaniacum (Roewer, 1914)), Trogulocratus tunetanus Roewer, 1950 syn. n. (=Calathocratus africanus (Lucas, 1849)), Trogulus albicerus Sø-rensen, 1873 syn. n. (=Calathocratus sinuosus (Sørensen, 1873)), Metopoctea exarata Simon, 1879a syn. n. (=Trogulus aquaticus Simon, 1879a), Trogulus galasensis Avram, 1971 syn. n. (=Trogulus nepaeformis (Scopoli, 1763)) and Trogulus roeweri Avram, 1971 syn. n. (=Trogulus nepaeformis (Scopoli, 1763)). Paranemastoma werneri (Kulczynski, 1903) is elevated from subspecies to species. Ischyropsalis luteipes Simon, 1872b is proposed as nomen protectum, taking precedence over Lhermia spinipes Lucas 1866 nomen oblitum. The same accounts for Anelasmocephalus cambridgei (Westwood, 1874) nomen protectum, taking precedence over Trogulus violaceus Gervais, 1844 nomen oblitum, Trogulus closanicus Avram, 1971 nomen protectum over Trogulus asperatus C.L. Koch, 1839a nomen oblitum, as well as Trogu-lus martensi Chemini, 1983 nomen protectum over Trogulus tuberculatus Canestrini, 1874 nomen oblitum. New combinations, all from Nemastoma, are Histricostoma anatolicum (Roewer, 1962), Mediostoma globuliferum (L. Koch, 1867), Nemastomella hankiewiczii (Kulczynski, 1909), Nemastomella maarebense (Simon, 1913), Nemastomella monchiquense (Kraus, 1961) and Paranemastoma simplex (Giltay, 1932); from Mitostoma: Nemastomella armatissima (Roewer, 1962). Revived combinations are Nemastomella cristinae (Rambla, 1969) (from Nemastoma) and Nemastomella sexmucronatum (Simon, 1911) (from Nemastoma). The following Nemastoma are transferred to Paranemastoma but suggested as nomina dubia: aeginum (Roewer, 1951), amuelleri (Roewer, 1951), bolei (Hadzi, 1973a), caporiaccoi (Roewer, 1951), carneluttii (Hadzi, 1973a), ferkeri (Roewer, 1951), gigas montenegrinum (Nosek, 1904), gostivarense (Hadzi, 1973a), ikarium (Roewer, 1951), quadripunctatum ios (Roewer, 1917), kaestneri (Roewer, 1951), longipalpatum (Roewer, 1951), macedonicum (Hadzi, 1973a), multisignatum (Hadzi, 1973a), nigrum (Hadzi, 1973a), perfugium (Roewer, 1951), santorinum (Roewer, 1951), senussium (Roewer, 1951), sketi (Hadzi, 1973a), spinosulum (L. Koch, 1869). Further suggested nomina dubia are Trogulus coreiformis C.L. Koch, 1839a, Trogulus lygaeiformis C.L. Koch, 1839a and Trogulus templetonii Westwood, 1833.

Molecular phylogeny of the harvestmen genus Sabacon (Arachnida: Opiliones: Dyspnoi) reveals multiple Eocene-Oligocene intercontinental dispersal events in the Holarctic.

We investigated the phylogeny and biogeographic history of the Holarctic harvestmen genus Sabacon, which shows an intercontinental disjunct distribution and is presumed to be a relatively old taxon. Molecular phylogenetic relationships of Sabacon were estimated using multiple gene regions and Bayesian inference for a comprehensive Sabacon sample. Molecular clock analyses, using relaxed clock models implemented in BEAST, are applied to date divergence events. Biogeographic scenarios utilizing S-DIVA and Lagrange C++ are reconstructed over sets of Bayesian trees, allowing for the incorporation of phylogenetic uncertainty and quantification of alternative reconstructions over time. Four primary well-supported subclades are recovered within Sabacon: (1) restricted to western North America; (2) eastern North American S. mitchelli and sampled Japanese taxa; (3) a second western North American group and taxa from Nepal and China; and (4) eastern North American S. cavicolens with sampled European Sabacon species. Three of four regional faunas (wNA, eNA, East Asia) are thereby non-monophyletic, and three clades include intercontinental disjuncts. Molecular clock analyses and biogeographic reconstructions support nearly simultaneous intercontinental dispersal coincident with the Eocene-Oligocene transition. We hypothesize that biogeographic exchange in the mid-Tertiary is likely correlated with the onset of global cooling, allowing cryophilic Sabacon taxa to disperse within and among continents. Morphological variation supports the divergent genetic clades observed in Sabacon, and suggests that a taxonomic revision (e.g., splitting Sabacon into multiple genera) may be warranted.

Phylogenomic resolution of paleozoic divergences in harvestmen (Arachnida, Opiliones) via analysis of next-generation transcriptome data.

Next-generation sequencing technologies are rapidly transforming molecular systematic studies of non-model animal taxa. The arachnid order Opiliones (commonly known as "harvestmen") includes more than 6,400 described species placed into four well-supported lineages (suborders). Fossil plus molecular clock evidence indicates that these lineages were diverging in the late Silurian to mid-Carboniferous, with some fossil harvestmen representing the earliest known land animals. Perhaps because of this ancient divergence, phylogenetic resolution of subordinal interrelationships within Opiliones has been difficult. We present the first phylogenomics analysis for harvestmen, derived from comparative RNA-Seq data for eight species representing all suborders. Over 30 gigabases of original Illumina short-read data were used in de novo assemblies, resulting in 50-80,000 transcripts per taxon. Transcripts were compared to published scorpion and tick genomics data, and a stringent filtering process was used to identify over 350 putatively single-copy, orthologous protein-coding genes shared among taxa. Phylogenetic analyses using various partitioning strategies, data coding schemes, and analytical methods overwhelmingly support the "classical" hypothesis of Opiliones relationships, including the higher-level clades Palpatores and Phalangida. Relaxed molecular clock analyses using multiple alternative fossil calibration strategies corroborate ancient divergences within Opiliones that are possibly deeper than the recorded fossil record indicates. The assembled data matrices, comprising genes that are conserved, highly expressed, and varying in length and phylogenetic informativeness, represent an important resource for future molecular systematic studies of Opiliones and other arachnid groups.

Rational design of a selective covalent modifier of G protein ßγ subunits.

G protein-coupled receptors transduce signals through heterotrimeric G protein Gα and Gßγ subunits, both of which interact with downstream effectors to regulate cell function. Gßγ signaling has been implicated in the pathophysiology of several diseases, suggesting that Gßγ could be an important pharmaceutical target. Previously, we used a combination of virtual and manual screening to find small molecules that bind to a protein-protein interaction "hot spot" on Gßγ and block regulation of physiological effectors. One of the most potent and effective compounds from this screen was selenocystamine. In this study, we investigated the mechanism of action of selenocystamine and found that selenocysteamine forms a covalent complex with Gßγ by a reversible redox mechanism. Mass spectrometry and site-directed mutagenesis suggest that selenocysteamine preferentially modifies GßCys204, but also a second undefined site. The high potency of selenocystamine in Gßγ inhibition seems to arise from both high reactivity of the diselenide group and binding to a specific site on Gß. Using structural information about the "hot spot," we developed a strategy to selectively target redox reversible compounds to a specific site on Gßγ using peptide carriers such as SIGCAFKILGY(-cysteamine) [SIGC(-cysteamine)]. Mass spectrometry and site-directed mutagenesis indicate that SIGC(-cysteamine) specifically and efficiently leads to cysteamine (half-cystamine) modification of a single site on Gß, likely GßCys204, and inhibits Gßγ more than a hundred times more potently than cystamine. These data support the concept that covalent modifiers can be specifically targeted to the Gßγ "hot spot" through rational incorporation into molecules that noncovalently bind to Gßγ.

Hidden Mediterranean diversity: assessing species taxa by molecular phylogeny within the opilionid family Trogulidae (Arachnida, Opiliones).

This is the first comprehensive study to evaluate the relationships between the western palearctic harvestman families Dicranolasmatidae, Trogulidae and Nemastomatidae with focus on the phylogeny and systematics of Trogulidae, using combined sequence data of the nuclear 28S rRNA and the mitochondrial cytochrome b gene. Bayesian analysis and Maximum parsimony do not reliably resolve Dicranolasma as distinct family but place it on a similar phylogenetic level as several lineages of Trogulidae. Nemastomatidae and Trogulidae turned out to be monophyletic, as did genera Anelasmocephalus and Trogulus within the Trogulidae. The genera Calathocratus, Platybessobius and Trogulocratus each appeared para or polyphyletic, respectively and are synonymized with Calathocratus. The monotypic genus Kofiniotis is well supported. We show molecular data to be in general concordance with taxa characterized by morphology. Molecular data are especially useful to calibrate morphological characters for systematic purposes within homogeneous taxa. In the majority of closely related valid species we show the lowest level of genetic distance to be not lower than 5%. By this threshold in terms of traditionally accepted species the estimated number of species turns out to be 1.5-2.4 times higher than previously believed. With respect to European fauna cryptic diversity in Trogulidae is obviously extraordinarily high and hitherto largely underestimated.

Evaluating docking methods for prediction of binding affinities of small molecules to the G protein betagamma subunits.

Several studies have suggested that disrupting interactions of the G protein betagamma subunits with downstream binding partners might be a valuable study for pharmaceutical development. Recently, small molecules have been found which bind to Gbetagamma with high apparent affinity in an enzyme-linked immunosorbent assay (ELISA), have demonstrated selective inhibition of interactions of Gbetagamma with downstream signaling partners, and have been shown to increase antinociceptive effects of morphine and inhibit inflammation in vivo. In this paper we examine several docking and scoring protocols for estimating binding affinities for a set of 830 ligands from the NCI diversity set to the Gbeta1gamma2 subunit and compared these with IC50s measured in a competition ELISA with a high-affinity peptidic ligand. The best-performing docking protocol used a consensus score and ensemble docking and resulted in a 6-fold enrichment of high-affinity compounds in the top-ranked 5% of the ligand data set.

G protein betagamma subunits as targets for small molecule therapeutic development.

G proteins mediate the action of G protein coupled receptors (GPCRs), a major target of current pharmaceuticals and a major target of interest in future drug development. Most pharmaceutical interest has been in the development of selective GPCR agonists and antagonists that activate or inhibit specific GPCRs. Some recent thinking has focused on the idea that some pathologies are the result of the actions of an array of GPCRs suggesting that targeting single receptors may have limited efficacy. Thus, targeting pathways common to multiple GPCRs that control critical pathways involved in disease has potential therapeutic relevance. G protein betagamma subunits released from some GPCRs upon receptor activation regulate a variety of downstream pathways to control various aspects of mammalian physiology. There is evidence from cell- based and animal models that excess Gbetagamma signaling can be detrimental and blocking Gbetagamma signaling has salutary effects in a number of pathological models. Gbetagamma regulates downstream pathways through modulation of enzymes that produce cellular second messengers or through regulation of ion channels by direct protein-protein interactions. Thus, blocking Gbetagamma functions requires development of small molecule agents that disrupt Gbetagamma protein interactions with downstream partners. Here we discuss evidence that small molecule targeting Gbetagamma could be of therapeutic value. The concept of disruption of protein-protein interactions by targeting a "hot spot" on Gbetagamma is delineated and the biochemical and virtual screening strategies for identification of small molecules that selectively target Gbetagamma functions are outlined. Evaluation of the effectiveness of virtual screening indicates that computational screening enhanced identification of true Gbetagamma binding molecules. However, further refinement of the approach could significantly improve the yield of Gbetagamma binding molecules from this screen that could result in multiple candidate leads for future drug development.

Validation of in vivo myocardial strain measurement by magnetic resonance tagging with sonomicrometry.

OBJECTIVES: This study was designed to validate strain measurements obtained using magnetic resonance tagging with spatial modulation of magnetization (SPAMM). We compared circumferential segment shortening measurements (%S) obtained using SPAMM to sonomicrometry %S in a canine model with (n = 28) and without (n = 3) coronary artery ligation. BACKGROUND: Magnetic resonance tagging enables noninvasive measurement of myocardial strain, but such strain measurements have not yet been validated in vivo. METHODS: Circumferential sonomicrometry crystal pairs were placed in apical myocardium at ischemic risk in ligation studies and in adjacent and remote myocardium. The %S was obtained from closely juxtaposed sonomicrometry and SPAMM sites. RESULTS: Paired data were available from 19 of 31 studies. Both methods distinguished remote from ischemic function effectively (p = 0.014 for SPAMM and p = 0.002 for sonomicrometry). SPAMM %S was similar to sonomicrometry %S in ischemic myocardium (2 +/- 3 vs. 0 +/- 3 p = 0.067) but was slightly higher than sonomicrometry %S in remote myocardium (11 +/- 10 vs. 7 +/- 5, p = 0.033). End-systolic (n = 30) and late systolic (n = 34) SPAMM %S correlated well with sonomicrometry %S (r = 0.84, p < 0.0001 and r = 0.88, p < 0.0001). CONCLUSIONS: Magnetic resonance tagging using SPAMM can quantitate myocardial strain in ischemic and remote myocardium. This study validates its application in scientific investigation and clinical assessment of patients with myocardial ischemia.

Ultrafast three-dimensional contrast-enhanced magnetic resonance angiography and imaging in the diagnosis of partial anomalous pulmonary venous drainage.

OBJECTIVES: The purpose of our study was to evaluate patients with suspected anomalous pulmonary veins (APVs) and atrial septal defects (ASDs) using fast cine magnetic resonance imaging (MRI) and ultrafast three-dimensional magnetic resonance angiography (MRA). BACKGROUND: Precise anatomic definition of anomalous pulmonary and systemic veins, and the atrial septum are prerequisites for surgical correction of ASDs. Cardiac catheterization and transesophageal echocardiography (TEE) are currently used to diagnose APVs, but did not provide complete information in our patients. METHODS: Twenty consecutive patients with suspected APVs were studied by MRA after inconclusive assessment by catheterization, TEE or both. The MRI images were acquired with a fast cine sequence and a novel ultrafast three-dimensional sequence before and after contrast injection. RESULTS: Partial anomalous pulmonary venous drainage was demonstrated in 16 of 20 patients and was excluded in four patients. Magnetic resonance imaging correctly diagnosed APVs and ASDs in all patients (100%) who underwent surgery. For the diagnosis of APVs, the MRI and catheterization results agreed in 74% of patients and the MRI and TEE agreed in 75% of patients. For ASDs, MRI agreed with catheterization and TEE in 53% and 83% of patients, respectively. CONCLUSIONS: Fast cine MRI with three-dimensional contrast-enhanced MRA provides rapid and comprehensive anatomic definition of APVs and ASDs in patients with adult congenital heart disease in a single examination.

Assessment of synchronized direct mechanical ventricular actuation in a canine model of left ventricular dysfunction.

Direct mechanical ventricular actuation (DMVA) is an experimental procedure that provides biventricular cardiac assistance by intracorporeal pneumatic compression of the heart. The advantages this technique has over other assist devices are biventricular assistance, no direct blood contact, pulsatile blood flow, and rapid, less complicated application. Prior studies of nonsynchronized DMVA support have demonstrated that a subject can be maintained for up to 7 days. The purpose of this study was to determine the acute hemodynamic effects of cardiac synchronized, partial DMVA support in a canine model (RVP) of left ventricular (LV) dysfunction. The study consisted of rapidly pacing seven dogs for 4 weeks to create LV dysfunction. At the conclusion of the pacing period, the DMVA device was positioned around the heart by means of a median sternotomy. The animals were then imaged in a 1.5 T whole body high speed clinical MR system, with simultaneous LV pressure recording. Left ventricular pressure-volume (PV) loops of the nonassisted and DMVA assisted heart were generated and demonstrated that DMVA assist shifted the loops leftward. In addition, assist significantly improved pressure dependent LV systolic parameters (left ventricular peak pressure and dp/dt max, p < 0.05), with no diastolic impairment. This study demonstrates that DMVA can provide synchronized partial assist, resulting in a decrease in the workload of the native heart, thus having a potential application for heart failure patients.

Origin of a signal intensity loss artifact in fat-saturation MR imaging.

Artifactual water signal intensity loss can be observed on fat-saturation magnetic resonance (MR) images of inhomogeneous regions such as the thorax. Magnetic effects of air inclusions on fat-saturation pulses were investigated as the possible origin of this artifact. Computer simulation results agreed well with observed production of water saturation by means of nominal fat suppression in MR imaging of phantoms and a representative clinical example.

Dynamic cardiomyoplasty decreases myocardial workload as assessed by tissue tagged MRI.

The effects of dynamic cardiomyoplasty (CMP) on global and regional left ventricular (LV) function in end-stage heart failure still remain unclear. MRI with tissue-tagging is a novel tool for studying intramyocardial motion and mechanics. To date, no studies have attempted to use MRI to simultaneously study global and regional cardiac function in a model of CMP. In this study, we used MRI with tissue-tagging and a custom designed MR compatible muscle stimulating/pressure monitoring system to assess long axis regional strain and displacement variations, as well as changes in global LV function in a model of dynamic cardiomyoplasty. Three dogs underwent rapid ventricular pacing (RVP; 215 BPM) for 10 weeks; after 4 weeks of RVP, a left posterior CMP was performed. After 1 year of dynamic muscle stimulation, the dogs were imaged in a 1.5 T clinical MR scanner. Unstimulated and muscle stimulated tagged long axis images were acquired. Quantitative 2-D regional image analysis was performed by dividing the hearts into three regions: apical, septal, and lateral. Maximum and minimum principal strains (lambda, and lambda2) and displacement (D) were determined and pooled for each region. MR LV pressure-volume (PV) loops were also generated. Muscle stimulation produced a leftward shift of the PV loops in two of the three dogs, and an increase in the peak LV pressure, while stroke volume remained unchanged. With stimulation, lambda1 decreased significantly (p<0.05) in the lateral region, whereas lambda2 increased significantly (p<0.05) in both the lateral and apical regions, indicating a decrease in strain resulting from stimulation. D only increased significantly (p<0.05) in the apical region. The decrease in strain between unassisted and assisted states indicates the heart is performing less work, while maintaining stroke volume and increasing peak LV pressure. These findings demonstrate that the muscle wrap functions as an active assist, decreasing the workload of the heart, while preserving total pump performance.