title: Myocardial perfusion cardiovascular magnetic resonance: optimized dual sequence and reconstruction for quantification.
abstract: BACKGROUND
  Quantification of myocardial blood flow requires knowledge of the amount of contrast agent in the myocardial tissue and the arterial input function (AIF) driving the delivery of this contrast agent. Accurate quantification is challenged by the lack of linearity between the measured signal and contrast agent concentration. This work characterizes sources of non-linearity and presents a systematic approach to accurate measurements of contrast agent concentration in both blood and myocardium.
  
  
  METHODS
  A dual sequence approach with separate pulse sequences for AIF and myocardial tissue allowed separate optimization of parameters for blood and myocardium. A systems approach to the overall design was taken to achieve linearity between signal and contrast agent concentration. Conversion of signal intensity values to contrast agent concentration was achieved through a combination of surface coil sensitivity correction, Bloch simulation based look-up table correction, and in the case of the AIF measurement, correction of T2* losses. Validation of signal correction was performed in phantoms, and values for peak AIF concentration and myocardial flow are provided for 29 normal subjects for rest and adenosine stress.
  
  
  RESULTS
  For phantoms, the measured fits were within 5% for both AIF and myocardium. In healthy volunteers the peak [Gd] was 3.5 ± 1.2 for stress and 4.4 ± 1.2 mmol/L for rest. The T2* in the left ventricle blood pool at peak AIF was approximately 10 ms. The peak-to-valley ratio was 5.6 for the raw signal intensities without correction, and was 8.3 for the look-up-table (LUT) corrected AIF which represents approximately 48% correction. Without T2* correction the myocardial blood flow estimates are overestimated by approximately 10%. The signal-to-noise ratio of the myocardial signal at peak enhancement (1.5 T) was 17.7 ± 6.6 at stress and the peak [Gd] was 0.49 ± 0.15 mmol/L. The estimated perfusion flow was 3.9 ± 0.38 and 1.03 ± 0.19 ml/min/g using the BTEX model and 3.4 ± 0.39 and 0.95 ± 0.16 using a Fermi model, for stress and rest, respectively.
  
  
  CONCLUSIONS
  A dual sequence for myocardial perfusion cardiovascular magnetic resonance and AIF measurement has been optimized for quantification of myocardial blood flow. A validation in phantoms was performed to confirm that the signal conversion to gadolinium concentration was linear. The proposed sequence was integrated with a fully automatic in-line solution for pixel-wise mapping of myocardial blood flow and evaluated in adenosine stress and rest studies on N = 29 normal healthy subjects. Reliable perfusion mapping was demonstrated and produced estimates with low variability.
authors.affiliation: National Heart, Lung, and Blood Institute, National Institutes of Health, DHHS, 10 Center Drive MSC-1061, Bethesda, MD, 20892, USA. kellman@nih.gov.
authors.forename: Peter
authors.identifier: http://orcid.org/0000-0002-9875-6070
authors.initials: P
authors.lastname: Kellman
authors.affiliation: National Heart, Lung, and Blood Institute, National Institutes of Health, DHHS, 10 Center Drive MSC-1061, Bethesda, MD, 20892, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hansen
authors.affiliation: National Heart, Lung, and Blood Institute, National Institutes of Health, DHHS, 10 Center Drive MSC-1061, Bethesda, MD, 20892, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Nielles-Vallespin
authors.affiliation: Department of Clinical Physiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jannike
authors.initials: J
authors.lastname: Nickander
authors.affiliation: Department of Clinical Physiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Raquel
authors.initials: R
authors.lastname: Themudo
authors.affiliation: Department of Clinical Physiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Ugander
authors.affiliation: National Heart, Lung, and Blood Institute, National Institutes of Health, DHHS, 10 Center Drive MSC-1061, Bethesda, MD, 20892, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Xue
mesh_terms: D000241:Adenosine / Q000008:administration & dosage; D001331:Automation; D001783:Blood Flow Velocity; D003287:Contrast Media / Q000008:administration & dosage; D003326:Coronary Circulation; D064368:Healthy Volunteers; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D055414:Myocardial Perfusion Imaging / Q000295:instrumentation / Q000379:methods*; D017711:Nonlinear Dynamics; D019047:Phantoms, Imaging; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D003287:Contrast Media; D014665:Vasodilator Agents; D000241:Adenosine
keywords: Arterial input function; Flow; Gadolinium; Myocardial perfusion; Perfusion quantification