Method and apparatus for noninvasive quantitative detection of fibrosis in the heart

Abstract

Embodiments provide a noninvasive quantitative method for detecting extent and/or types of fibrosis in the heart. In embodiments, information pertaining to the extent and/or types of fibrosis may aid in the diagnosis of specific cardiac diseases and heart failure and/or may assist in determining suitable treatment options. Embodiments provide methods and apparatuses for determining the extent of fibrosis in viable and nonviable myocardium, which may then be correlated to heart disease and failure. Thus, in an embodiment, a method of screening individuals for the purpose of heart disease or heart failure prevention may be provided using the detection methodology described herein.

1 . A method of detecting fibrosis in heart tissue, comprising:
 selecting a sample of viable or nonviable heart tissue;   contacting the sample with an extracellular contrast agent;   obtaining one or more measurements of the contrast uptake of the sample with an imaging apparatus to determine an extent of expansion of extracellular volume in the sample as an indicator of diffuse interstitial and/or replacement fibrosis.   
   
   
       2 . The method of  claim 1 , wherein contacting the sample with an extracellular contrast agent comprises contacting the sample with a Gadolinium-containing contrast agent. 
   
   
       3 . The method of  claim 1 , wherein contacting the sample with an extracellular contrast agent comprises contacting the sample with gadodiamide. 
   
   
       4 . The method of  claim 1 , wherein contacting the sample with an extracellular contrast agent comprises contacting the sample with an extracellular collagen-binding contrast agent. 
   
   
       5 . The method of  claim 1 , wherein contacting the sample with an extracellular contrast agent comprises contacting the sample in-vivo with an extracellular contrast agent. 
   
   
       6 . The method of  claim 1 , wherein contacting the sample with an extracellular contrast agent comprises contacting the sample in-vitro with an extracellular contrast agent. 
   
   
       7 . The method of  claim 1 , wherein obtaining one or more images of the sample comprises obtaining one or more images using magnetic resonance imaging. 
   
   
       8 . The method of  claim 7 , wherein obtaining one or more images using magnetic resonance imaging comprises performing a plurality of T1 relaxation time measurements in blood and in the sample, both before and after contact with one or more contrast agents to determine the tissue sample partition coefficient for the extracellular contrast agent. 
   
   
       9 . The method of  claim 8 , wherein the relaxation times (T1) are converted into relaxation rates with R1=1/T1, and wherein each R1 rate determined for the sample is linearly regressed against a determined R1 rate in the blood. 
   
   
       10 . The method of  claim 8 , further comprising obtaining a blood hematocrit, and wherein the sample partition coefficient and the blood hematocrit are used to calculate the extracellular volume in the tissue sample. 
   
   
       11 . The method of  claim 7 , wherein obtaining one or more images using magnetic resonance imaging comprises performing rapid imaging before, during and after contrast agent contact to measure contrast enhancement in the sample and in blood resident in a ventricular cavity or one or more large vessels. 
   
   
       12 . The method of  claim 11 , wherein dynamics of contrast enhancement are analyzed with a two-space model to determine the extracellular volume in the sample. 
   
   
       13 . The method of  claim 1 , further comprising creating parametric maps of the extracellular volume as a marker of fibrosis. 
   
   
       14 . The method of  claim 1 , further comprising determining a global diffuse fibrosis burden in the sample. 
   
   
       15 . The method of  claim 1 , further comprising classifying an extent of diffuse fibrosis in a patient from which the sample is selected to determine risk of heart failure or heart disease. 
   
   
       16 . The method of  claim 1 , further comprising determining and distinguishing between an extent of interstitial and an extent of replacement fibrosis in the sample. 
   
   
       17 . The method of  claim 1 , wherein obtaining one or more images of the sample comprises obtaining one or more images using computed x-ray tomography. 
   
   
       18 . The method of  claim 1 , further comprising determining the presence of, location of, and/or extent of interstitial and replacement fibrosis in a tissue sample or whole heart and correlating the determination with a heart condition, disease, or associated risk of a particular heart disease or failure. 
   
   
       19 . The method of  claim 18 , wherein correlating the determination with a heart condition, disease, or associated risk of a particular heart disease or failure is represented as a numeric or textual risk factor.