Methods for monitoring tight clot formation
The invention features a method of monitoring a clotting process by measuring a signal characteristic of the NMR relaxation of water in a sample undergoing clotting to produce NMR relaxation data and determining from the NMR relaxation data a magnetic resonance parameter of water in the sample characteristic of the clots being formed.
1. A method of monitoring a clotting or dissolution process in a first blood sample comprising:
(i) making a series of magnetic resonance relaxation rate measurements of water in said blood sample at a series of time points during said process;
(ii) transforming said measurements using an algorithm that distinguishes two or more separate water populations within said first blood sample at one or more of said time points, wherein the two or more water populations comprise a water population having a serum-associated T2 signal and a water population having a tightly bound clot-associated T2 signal, and wherein the serum-associated T2 signal and the clot-associated T2 signal are separately characterized by one or more magnetic resonance parameters having one or more values; and
(iii) on the basis of the results of step (ii), determining whether a tightly bound clot is formed or dissolved during said process.
2. The method of claim 1 , wherein said first blood sample is a platelet rich plasma sample, a whole blood sample, or a clotted blood sample.
3. The method of claim 1 , wherein prior to step (i), to said first blood sample is added fibrinogen.
4. The method of claim 1 , wherein prior to, or after, step (i), to said first blood sample is added a clotting initiator or a clotting inhibitor.
5. The method of claim 4 , wherein to said first blood sample is added a clotting initiator selected from RF, AA, ADP, CK, TRAP, epinephrine, collagen, tissue factor, celite, ellagic acid, and thrombin; or wherein to said first blood sample is added a clotting inhibitor that is a platelet aggregation inhibitor; or wherein prior to step (i), to said first blood sample is added tissue plasminogen activator (TPA), aprotinin, Abciximab (Reopro), or Cytochalasin-D.
6. The method of claim 1 , wherein said algorithm comprises an algorithm selected from the group consisting of a multi-exponential algorithm, a bi-exponential algorithm, a tri-exponential algorithm, a decaying exponential algorithm, a Laplace transform, an Inverse Laplace Transform, a goodness-of-fit algorithm, an SSE algorithm, a least squares algorithm, and a non-negative least squares algorithm.
7. The method of claim 1 , wherein said water population having a tightly bound clot-associated T2 signal is characterized by a T2 relaxation rate in the range of 40 to 250 ms; or wherein said two or more water populations further comprise a water population having a clot-associated T2 signal.
8. The method of claim 6 , wherein said relaxation rate measurements comprise a T2 measurement, and wherein said measurement provides a decay curve.
9. The method of claim 8 , further comprising calculating from said decay curve a T2 relaxation spectrum at a predetermined time point following initiation of said clotting or dissolution process.
10. The method of claim 9 , further comprising, following initiation of a clotting or dissolution process in a blood sample, (a) making a plurality of relaxation rate measurements on said blood sample during said process to produce a plurality of decay curves, and (b) calculating from said plurality of decay curves a plurality of T2 relaxation spectra.