title: T2 magnetic resonance: a diagnostic platform for studying integrated hemostasis in whole blood--proof of concept.
abstract: BACKGROUND
  Existing approaches for measuring hemostasis parameters require multiple platforms, can take hours to provide results, and generally require 1-25 mL of sample. We developed a diagnostic platform that allows comprehensive assessment of hemostatic parameters on a single instrument and provides results within 15 min using 0.04 mL of blood with minimal sample handling.
  
  
  METHODS
  T2 magnetic resonance (T2MR) was used to directly measure integrated reactions in whole blood samples by resolving multiple water relaxation times from distinct sample microenvironments. Clotting, clot contraction, and fibrinolysis stimulated by thrombin or tissue plasminogen activator, respectively, were measured. T2MR signals of clotting samples were compared with images produced by scanning electron microscopy and with standard reference methods for the following parameters: hematocrit, prothrombin time, clot strength, and platelet activity.
  
  
  RESULTS
  Application of T2MR methodology revealed conditions under which a unique T2MR signature appeared that corresponded with the formation of polyhedral erythrocytes, the dynamics and morphology of which are dependent on thrombin, fibrinogen, hematocrit, and platelet levels. We also showed that the T2MR platform can be used for precise and accurate measurements of hematocrit (%CV, 4.8%, R(2) = 0.95), clotting time (%CV, 3.5%, R(2) = 0.94), clot strength (R(2) = 0.95), and platelet function (93% agreement with light transmission aggregometry).
  
  
  CONCLUSIONS
  This proof-of-concept study demonstrates that T2MR has the potential to provide rapid and sensitive identification of patients at risk for thrombosis or bleeding and to identify new biomarkers and therapeutic targets with a single, simple-to-employ analytic approach that may be suitable for routine use in both research and diverse clinical settings.
authors: T2 Biosystems, Lexington, MA;
authors: Lynell R
authors: LR
authors: Skewis
authors: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors: Tatiana
authors: T
authors: Lebedeva
authors: T2 Biosystems, Lexington, MA;
authors: Vyacheslav
authors: V
authors: Papkov
authors: T2 Biosystems, Lexington, MA;
authors: Edward C
authors: EC
authors: Thayer
authors: T2 Biosystems, Lexington, MA;
authors: Walter
authors: W
authors: Massefski
authors: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors: Adam
authors: A
authors: Cuker
authors: Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors: Chandrasekaran
authors: C
authors: Nagaswami
authors: Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors: Rustem I
authors: RI
authors: Litvinov
authors: Institute of Medical Biology, Polish Academy of Science, Lodz, Poland; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
authors: M Anna
authors: MA
authors: Kowalska
authors: Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
authors: Lubica
authors: L
authors: Rauova
authors: Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
authors: Mortimer
authors: M
authors: Poncz
authors: Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors: John W
authors: JW
authors: Weisel
authors: T2 Biosystems, Lexington, MA; tlowery@t2biosystems.com.
authors: Thomas J
authors: TJ
authors: Lowery
authors: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors: Douglas B
authors: DB
authors: Cines
mesh_terms: D001777:Blood Coagulation / Q000502:physiology; D006400:Hematocrit; D006402:Hematologic Diseases / Q000097:blood*; D006487:Hemostasis; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D012680:Sensitivity and Specificity; D013997:Time Factors; D051598:Whole Body Imaging