64 research outputs found
Myocardial perfusion in heart disease
Get PDFHeart disease: Coronary heart disease is a major cause of mortality and morbidity in the UK and globally. It is managed with medical therapy and coronary revascularisation to reduce symptoms and reduce risk of major adverse cardiovascular events. When patients present with chest pain, it is important to risk stratify those that would most benefit from invasive coronary assessment and those that can be managed with medical therapy alone. Myocardial perfusion techniques have been developed in order to do this.
Cardiovascular magnetic resonance (CMR) with stress perfusion: CMR allows the non-invasive assessment of coronary artery disease (CAD). Under conditions of vasodilator stress, a gadolinium based contrast agent is injected and during the first pass through the left ventricle, perfusion defects can be observed. There is a strong evidence base for perfusion CMR but the technique is qualitative, relies on experienced operators and potentially misses globally low perfusion such as in cases of “balanced” ischaemia.
Quantitative perfusion CMR: In contrast, quantitative perfusion techniques allow the calculation of myocardial blood flow (MBF). It is more objective, less reliant on the expert observer and can give additional insights into microvascular disease and cardiomyopathy. As well as being less subjective, quantitative perfusion has other advantages for example it allows full assessment of ischaemic burden and may contain prognostic information that could be used to risk stratify and improve patient care. However, quantitative perfusion has been outside the realm of routine clinical practice due to difficulties in acquiring suitable data for full quantification and the laborious nature of analysing it.
Perfusion mapping: Peter Kellman, Hui Xue and colleagues at the National Institutes for Health, USA developed the “perfusion mapping” technique to address these limitations. Perfusion maps are generated automatically and inline during the CMR scan and each voxel encodes myocardial blood flow. This allows the instant quantification of MBF without complex acquisition techniques and post processing. In this thesis I have taken perfusion mapping and deployed in the real-world at a scale an order of magnitude higher than prior quantitative perfusion studies, developing the evidence base for routine clinical use across a broad range of diseases and scenarios:
In coronary artery disease: I have shown that perfusion mapping is accurate to detect coronary artery stenosis as defined by 3D quantitative coronary angiography in a single centre, 50 patient study. Transmural and subendocardial perfusion are particularly sensitive to detect coronary stenoses with performances similar to expert readers. There is a high sensitivity and high negative predictive value making perfusion mapping a good “rule-out” test for coronary disease.
Quantitative perfusion and prognosis: I investigated whether stress MBF and myocardial perfusion reserve (MPR) calculated by perfusion mapping would encode prognostic information in a 1049 patient multi-centre study over a mean follow up time of 605 days. Both stress MBF and MPR were independently associated with death and major adverse cardiovascular events (MACE). The hazard ratio for MACE was 2.14 for each 1ml/g/min decrease in stress MBF and 1.74 for each unit decrease in MPR. This work can now be taken forward with prospective studies in order to better risk stratify patients, including those without perfusion defects on clinical read.
Reference ranges and non-obstructive coronary disease: I sought to determine the factors that contribute to perfusion in a multi-centre registry study. In patients with no obstructive coronary artery disease, stress MBF was reduced with age, diabetes, left ventricular hypertrophy (LVH) and the use of beta blockers. Rest MBF was influenced by sex (higher in females) and reduced with beta blockers. This study suggests patient factors beyond coronary artery disease (and therefore likely microvascular disease) should also be considered when interpreting quantitative perfusion studies.
In cardiomyopathy: I also investigated myocardial perfusion in cardiomyopathy looking at Fabry disease as an example disease. In a prospective, observational, single centre study of 44 patients and 27 controls I found Fabry patients had reduced perfusion (and therefore likely microvascular dysfunction), particularly in the subendocardium and was associated with left ventricular hypertrophy (LVH), glycophospholipid storage and scar. Perfusion was reduced even in patients without LVH suggesting it is an early disease marker.
In conclusion, in this thesis, I have developed an evidence base for quantitative perfusion CMR and demonstrated how it can be integrated into routine clinical care. Perfusion mapping is accurate for detecting coronary artery stenosis and encodes prognostic information. Further work in this area could enable patients to be risk stratified based on their myocardial perfusion in order to reduce the morbidity and mortality associated with epicardial and microvascular coronary artery disease. Following on from this work, two further British Heart Foundation Clinical Research Training Fellowships have been awarded to further investigate quantitative perfusion in patients following surgical revascularisation of coronary disease and in patients with hypertrophic cardiomyopathy
Ultrafast extreme ultraviolet spectroscopy of transition metal dithiolate coordination complexes
Get PDFTransient tabletop M-edge x-ray absorption near edge structure (XANES) spectroscopy using extreme ultraviolet (XUV) light is used as a tool to interrogate the evolution of the metal center in a series of transition metal dithiolate complexes. The behavior of these molecules after absorption of light has implications for the development of catalysts and photosensitizers using earth-abundant transition metals. The cobalt dithiolene complex, [Co(bdt)2]- (bdt = 1,2-benzendithiolate), is primarily known for its ligand-noninnocence and participation in the catalytic production of hydrogen. After excitation of [Co(bdt)2]- with visible light, its relaxation dynamics are tracked with a combination of optical and transient M-edge XANES spectroscopic techniques that allow for the identification of a ligand-to-metal charge transfer (LMCT) excited state whose spin can be determined by comparison to semi-empirical ligand field multiplet calculations. The combination of optical and x-ray techniques is crucial to identifying relaxation processes that affect predominantly either the metal or the ligand. NEVPT2 calculations are used to understand its optical absorption spectrum and rationalize the timescale by which the molecule relaxes to the ground state. A set of three of cobalt tris(dithiolate) complexes with varying ligand field strength have been studied using optical transient absorption spectroscopy which shows a difference of a factor of at least ten in their excited state lifetimes. Understanding the origin of this change is important to further extending the lifetimes of photosensitizers. The sensitivity of M-edge XANES spectroscopy to the oxidation and spin state of a metal enabled the identification of the excited states involved in the relaxation of all three complexes. The contribution of a long-lived charge transfer state was ruled out and the final excited state was determined to be a 5T state. Finally, a nickel dithiocarbamate complex, Ni(dedtc)2 (dedtc = diethyldithiocarbamate, S2CNEt2) was studied as a simple analogue of a square planar nickel-centered hydrogen catalyst. Examination of this complex and the equivalent copper and zinc complexes reveal new phenomena in XUV spectroscopy, including dependence of the ligand absorbance on the metal center and observation of a ligand-based change in absorbance beneath the nickel M-edge after LMCT excitation.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2023-05-01The student, Kristopher Benke, accepted the attached license on 2021-04-12 at 10:11.The student, Kristopher Benke, submitted this Dissertation for approval on 2021-04-12 at 10:46.This Dissertation was approved for publication on 2021-04-14 at 11:42.DSpace SAF Submission Ingestion Package generated from Vireo submission #16283 on 2021-09-16 at 17:02:51Made available in DSpace on 2021-09-17T02:34:23Z (GMT). No. of bitstreams: 3
BENKE-DISSERTATION-2021.pdf: 2425264 bytes, checksum: 1309f977d92270d74397cd3146a8dc91 (MD5)
Benke_Kristopher_Dissertation.docx: 11158473 bytes, checksum: af803d0e32292daaea82fd2150cede26 (MD5)
LICENSE.txt: 4213 bytes, checksum: e4b94f96dec9482c464d7086c4182278 (MD5)
Previous issue date: 2021-04-14Embargo set by: Seth Robbins for item 118497
Lift date: 2023-09-17T02:34:57Z
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemAuthor requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemU of I Onl
Neutrino events at IceCube and the Fermi bubbles
Get PDFabstract: We discuss the possibility that the IceCube neutrino telescope might be observing the Fermi bubbles. If the bubbles discovered in gamma rays originate from accelerated protons, they should be strong emitters of high energy (≳ GeV) neutrinos. These neutrinos are detectable as showerlike or tracklike events at a Km[superscript 3] neutrino observatory. For a primary cosmic ray flux with spectrum ∝ E[superscript −2.1] and cutoff energy at or above 10 PeV, the Fermi bubble flux substantially exceeds the atmospheric background, and could account for up to ∼4–5 of the 28 events detected above ∼30 TeV at IceCube. Running the detector for ∼5–7 more years should be sufficient to discover this flux at high significance. For a primary cosmic ray flux with steeper spectrum, and/or lower cutoff energy, longer running times will be required to overcome the background.Copyright 2014 by the American Physical Society. View the article as published at http://dx.doi.org/10.1103/PhysRevD.90.02301
Corrigendum
Get PDFAuthor Posting. © American Meteorological Society, 2014. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Atmospheric and Oceanic Technology 31 (2014): 2871, doi:10.1175/JTECH-D-14-00187.1
A role for the equatorial undercurrent in the ocean dynamical thermostat
Get PDFAuthor Posting. © American Meteorological Society, 2018. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 31 (2018): 6245-6261, doi:10.1175/JCLI-D-17-0513.1.Reconstructions of sea surface temperature (SST) based on instrumental observations suggest that the equatorial Pacific zonal SST gradient has increased over the twentieth century. While this increase is suggestive of the ocean dynamical thermostat mechanism of Clement et al., observations of a concurrent weakening of the zonal atmospheric (Walker) circulation are not. Here we show, using heat and momentum budget calculations on an ocean reanalysis dataset, that a seasonal weakening of the zonal atmospheric circulation is in fact consistent with cooling in the eastern equatorial Pacific (EEP) and thus an increase in the zonal SST gradient. This cooling is driven by a strengthening Equatorial Undercurrent (EUC) in response to decreased upper-ocean westward momentum associated with weakening equatorial zonal wind stress. This process can help to reconcile the seemingly contradictory twentieth-century trends in the tropical Pacific atmosphere and ocean. Moreover, it is shown that coupled general circulation models (CGCMs) do not correctly simulate this process; we identify a systematic bias in the relationship between changes in equatorial surface zonal wind stress in the EEP and EUC strength that may help to explain why observations and CGCMs have opposing trends in the zonal SST gradient over the twentieth century.2019-01-1
An equatorial ocean bottleneck in global climate models
Get PDFAuthor Posting. © American Meteorological Society, 2012. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 25 (2012): 343–349, doi:10.1175/JCLI-D-11-00059.1.The Equatorial Undercurrent (EUC) is a major component of the tropical Pacific Ocean circulation. EUC velocity in most global climate models is sluggish relative to observations. Insufficient ocean resolution slows the EUC in the eastern Pacific where nonlinear terms should dominate the zonal momentum balance. A slow EUC in the east creates a bottleneck for the EUC to the west. However, this bottleneck does not impair other major components of the tropical circulation, including upwelling and poleward transport. In most models, upwelling velocity and poleward transport divergence fall within directly estimated uncertainties. Both of these transports play a critical role in a theory for how the tropical Pacific may change under increased radiative forcing, that is, the ocean dynamical thermostat mechanism. These findings suggest that, in the mean, global climate models may not underrepresent the role of equatorial ocean circulation, nor perhaps bias the balance between competing mechanisms for how the tropical Pacific might change in the future. Implications for model improvement under higher resolution are also discussed.KBK gratefully acknowledges the J. Lamar
Worzel Assistant Scientist Fund. GCJ is supported by
NOAA’s Office of Oceanic and Atmospheric Research. RM gratefully acknowledges the generous support
and hospitality of the Divecha Centre for Climate
Change and CAOS at IISc, Bangalore, and partial support
by NASA PO grants.2012-07-0
A changing heart in tako-tsubo syndrome
No full textA 63-year-old female presented with acute chest pain and ECG showing T wave inversion in the anterior and inferior leads. Troponin T (TnT) was significantly elevated (peak 1378 ng/L; normal <14 ng/L), as was NT-proBNP (3091 ng/L; normal <400 ng/L). Invasive angiography showed unobstructed coronary arteries with mid-ventricular ballooning and hypokinesia on ventriculography (see Supplementary data online, Video S1) and echocardiography (see Supplementary data online, Video S2), suggesting a mid-ventricular tako-tsubo syndrome (TTS). Cardiac magnetic resonance (CMR) was booked but the patient was unable to attend. Focussed history using the InterTAK diagnostic score assessment revealed no emotional or physical triggers. The patient re-presented six months later with similar symptoms and elevated TnT. Inpatient echocardiography showed a reverse TTS pattern (see Supplementary data online, Video S3) and CMR at 1.5T showed basal hypokinesia with matching elevated native T1 (1220 ms; normal 950–1100 ms) and T2 (69 ms; normal <48 ms) (Panels A–B). Quantitative perfusion maps following adenosine stress perfusion to investigate microvascular disease showed basal to mid circumferential hypoperfusion with normal apical myocardial blood flow, not suggestive of specific coronary artery territory ischaemia (Panel D) and no late gadolinium enhancement (LGE) (Panel C), confirming a reverse TTS. The patient further presented two months later with chest pain and TnT elevation. Repeat inpatient CMR on this occasion showed a classic TTS pattern with apical hypokinesia and elevated T1 and T2 (1261 ms and 81 ms, respectively) at the mid to apical segments with no LGE (Panels E–G). The case was further explored but no triggers, including neurological or psychiatric abnormalities were found. Recurrent TTS with different phenotypes has previously been described but is rare, especially without a trigger. Our case illustrates the utility of multimodality imaging in the investigation of TTS; in particular, multiparametric tissue mapping by CMR. Furthermore, the novel quantitative perfusion maps characterising myocardial blood flow added diagnostic utility
Review of \u3cem\u3eThe Loyal West: Civil War and Reunion in Middle America\u3c/em\u3e by Matthew E. Stanley
Get PDFInterest in Civil War memory and post–Civil War sectional reconciliation has expanded greatly in recent years, as two 2016 historiographical essays attest.1 Matthew E. Stanley\u27s new book, The Loyal West: Civil War and Reunion in Middle America is thus well timed to make an important contribution to our evolving understanding of the process of sectional reconciliation in the decades following the Civil War. With his focus on Kentucky\u27s northern neighbors in the lower portions of Illinois, Indiana, and Ohio, the editorial staff of the Register of the Kentucky Historical Society believe Stanley\u27s book will help historians better understand the role Kentucky played in the events of the late nineteenth and early twentieth century, which saw a white supremacist version of Civil War memory eclipse an emancipationist version nationally.
We have asked four nineteenth-century historians to consider Stanley\u27s book from varying perspectives. M. Keith Harris teaches history at a private high school in Los Angeles, California. He is the author of Across the Bloody Chasm: The Culture of Commemoration among Civil War Veterans (2014) and is currently writing a book on D. W. Griffith\u27s controversial 1915 silent film, The Birth of a Nation. Anne E. Marshall is an associate professor of history at Mississippi State University and the author of Creating a Confederate Kentucky: The Lost Cause and Civil War Memory in a Border State (2012). James Marten is professor and chair of the history department at Marquette University. His most recent books are Sing Not War: The Lives of Union and Confederate Veterans in Gilded Age America (2011) and America\u27s Corporal: James Tanner in War and Peace (2014). Kristopher Maulden is a visiting assistant professor of history at Columbia College in Missouri. He is completing a book manuscript on the influence of Federalist politics and federal policy in the Ohio River Valley, and he is engaged in a study of nineteenth-century Ohio newspaper editor Charles Hammond. Finally, the author of The Loyal West, Matthew E. Stanley, assistant professor of history at Albany State University, will respond to the reviews
The Equatorial Undercurrent and TAO sampling bias from a decade at SEA
Get PDFAuthor Posting. © American Meteorological Society, 2014. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Atmospheric and Oceanic Technology 21 (2014): 2015–2025, doi:10.1175/JTECH-D-13-00262.1.The NOAA Tropical Atmosphere Ocean (TAO) moored array has, for three decades, been a valuable resource for monitoring and forecasting El Niño–Southern Oscillation and understanding physical oceanographic as well as coupled processes in the tropical Pacific influencing global climate. Acoustic Doppler current profiler (ADCP) measurements by TAO moorings provide benchmarks for evaluating numerical simulations of subsurface circulation including the Equatorial Undercurrent (EUC). Meanwhile, the Sea Education Association (SEA) has been collecting data during repeat cruises to the central equatorial Pacific Ocean (160°–126°W) throughout the past decade that provide useful cross validation and quantitative insight into the potential for stationary observing platforms such as TAO to incur sampling biases related to the strength of the EUC. This paper describes some essential sampling characteristics of the SEA dataset, compares SEA and TAO velocity measurements in the vicinity of the EUC, shares new insight into EUC characteristics and behavior only observable in repeat cross-equatorial sections, and estimates the sampling bias incurred by equatorial TAO moorings in their estimates of the velocity and transport of the EUC. The SEA high-resolution ADCP dataset compares well with concurrent TAO measurements (RMSE = 0.05 m s−1; R2 = 0.98), suggests that the EUC core meanders sinusoidally about the equator between ±0.4° latitude, and reveals a mean sampling bias of equatorial measurements (e.g., TAO) of the EUC’s zonal velocity of −0.14 ± 0.03 m s−1 as well as a ~10% underestimation of EUC volume transport. A bias-corrected monthly record and climatology of EUC strength at 140°W for 1990–2010 is presented.The authors thank the NSF
Physical Oceanography program (OCE-1233282) and
the WHOI Academic Programs Office for funding.2015-03-0
- …
