Dynamic MR Imaging of Patients with Breast Cancer - Establishment and Comparison of Different Analytical Methods for Tissue Perfusion and Capillary Permeability

Abstract

The present invention encompasses methods, apparatus, and computer based systems for identifying benign and malignant tumors in tissues such as soft tissues and particularly breast tissue using dynamic contrast-enhanced magnetic resonance imagining (DCE-MRI) and dynamic susceptibility contrast-enhanced magnetic resonance (DSC) imagining of the tumors. Some embodiments encompass the use of two dynamic MRI pulse sequences in intercalating mode during parenteral administration of an MR contrast substance, wherein one of said pulse sequences is optimized for spatial information and the other pulse sequence is adjusted for high temporal solution, the high-temporal dissolved sequence further comprising a double echo-collection sensitive towards both DCE and DSC for generating a number of different biomarker data such as pharmacokinetic biomarker data, descriptive DCE biomarkers and descriptive DSC biomarkers, and subsequently normalizing and comparing said data with corresponding data from corresponding benign and malign tumors, respectively.

1 - 12 . (canceled) 
     
     
         13 . A method for interpreting contrast magnetic resonance imaging (MRI) data from a soft tissue tumor in a subject comprising:
 a. comparing at least two biomarkers selected from TTP, R2*, Peak enh , R2*-peak enh , wash out rate, AUC, K trans , k ep , v p , and v e  with corresponding measurements for known malignant and benign tumors;
 wherein said biomarkers are derived from DCE-MRI and DSC-MRI imaging data obtained using at least two dynamic MRI pulse sequences comprising a pulse sequence optimized for high spatial resolution and a pulse sequence optimized for high temporal resolution; and 
 wherein at least one selected biomarker is determined using DCE-MRI imaging data and at least one selected biomarker is determined using DCS-MRI imaging data, optionally in combination with DCE-MRI imaging data; and 
   b. identifying the tumor as malignant or benign based on the selected biomarkers.   
     
     
         14 . The method of  claim 13 , wherein the pulse sequence optimized for high spatial resolution is T1-weighted. 
     
     
         15 . The method of  claim 13 , wherein the pulse sequence optimized for high temporal resolution gives two gradient echoes comprising a T1-weighted echo and a T2*-weighted echo. 
     
     
         16 . The method of  claim 13 , wherein the at least two biomarkers selected from wash out rate, TTP, quantitative K ep , quantitative v p , normalized K trans , normalized k ep , normalized v p , R2*-peak enh , and AUC. 
     
     
         17 . The method of  claim 13 , wherein the selected biomarkers comprise TTP and R2*-peak enh . 
     
     
         18 . The method of  claim 13 , wherein the selected biomarkers comprise TTP, R2*-peak enh , and normalized K. 
     
     
         19 . The method of  claim 13 , wherein the selected biomarkers comprise TTP, R2*-peak enh , and quantitative v p . 
     
     
         20 . The method of  claim 13 , wherein said soft tissue tumor is a breast tumor. 
     
     
         21 . The method of  claim 13 , wherein the tumor is further identified as invasive ductal carcinoma (IDC) or fibroadenoma (FA) by comparing at least one biomarker recited in step a with corresponding measurements for IDC and FA tumors. 
     
     
         22 . The method of  claim 21 , wherein the at least one biomarker is selected from TTP, R2*-peak enh , K trans , peak enh , kep, v p , and v e . 
     
     
         23 . The method of  claim 21 , wherein the at least one biomarker is selected from wash-out rate, TTP, AUC, Peak enh , normalized K trans , normalized v e , normalized v p , qualitative k ep , qualitative v e , and R2*-peak enh . 
     
     
         24 . The method of  claim 21 , wherein the at least one biomarker is selected from TTP, R2*-peak enh , and normalized K trans . 
     
     
         25 . An apparatus for analyzing a soft tissue tumor in a subject comprising:
 a. means for generating magnetic resonance sequence pulses, comprising a pulse sequence optimized for high spatial resolution and a sequence pulse optimized for high temporal resolution;   b. means for collecting contrast-enhanced DCE-MRI and DSC-MRI imaging data from the tumor;   c. means for analyzing the DCE-MRI and DSC-MRI imaging data to determine at two biomarkers selected from: TTP, R2*, Peak enh , R2*-peak enh , wash out rate, AUC, K trans , k ep , v p , and v e ;
 wherein at least one selected biomarker is determined using DCE-MRI imaging data and at least one selected biomarker is determined using DCS-MRI imaging data, optionally in combination with DCE-MRI imaging data; and 
   d. means for comparing the selected biomarkers with corresponding measurements for known malignant and benign tumors.   
     
     
         26 . The apparatus of  claim 25 , wherein the pulse sequence optimized for high spatial resolution is T1-weighted. 
     
     
         27 . The apparatus of  claim 25 , wherein the pulse sequence optimized for high temporal resolution gives two gradient echoes comprising a T1-weighted echo and a T2*-weighted echo. 
     
     
         28 . The apparatus of  claim 25 , wherein the at least two biomarkers selected from wash out rate, TTP, quantitative k ep , quantitative v p , normalized K trans , normalized k ep , normalized v p , R2*-peak enh , and AUC. 
     
     
         29 . The apparatus of  claim 25 , wherein the selected biomarkers comprise UP and R2*-peak enh . 
     
     
         30 . The apparatus of  claim 25 , wherein the selected biomarkers comprise UP, R2*-peak enh , and normalized K trans . 
     
     
         31 . The apparatus of  claim 25 , wherein the selected biomarkers comprise TTP, R2*-peak enh , and quantitative v p . 
     
     
         32 . The apparatus of  claim 25 , wherein said soft tissue tumor is a breast tumor. 
     
     
         33 . The apparatus of  claim 25 , further comprising means for comparing a second set of biomarkers with corresponding measurements for invasive ductal carcinoma (IDC) or fibroadenoma (FA). 
     
     
         34 . The apparatus of  claim 25 , wherein the second set of biomarkers is selected from UP, R2*-peak enh , K trans , peak enh , k ep , v p , and v e . 
     
     
         35 . The apparatus of  claim 25 , wherein the second set of biomarkers is selected from wash-out rate, UP, AUC, Peak enh , normalized K trans , normalized v e , Normalized v p , qualitative k ep , qualitative v e , and R2*-peak enh . 
     
     
         36 . The apparatus of  claim 25 , wherein the second set of biomarkers comprise TTP, R2*-peak enh , and normalized K trans . 
     
     
         37 . The method of  claim 13 , further comprising,
 a. collecting DWI imaging data from the tumor;   b. analyzing the DWI imaging data to determine at least one biomarker for tissue diffusion; and   c. comparing the selected DWI biomarker with corresponding measurements for known malignant and benign tumors to identify the tumor as malignant or benign.   
     
     
         38 . A computer-based system for analyzing soft tissue tumor in a subject comprising:
 a. means for analyzing the DCE-MRI and DSC-MRI imaging data to determine at two biomarkers selected from: TTP, R2*, Peak enh , R2*-peak enh , wash out rate, AUC, K trans , k ep , v p , and v e ;
 wherein at least one selected biomarker is determined using DCE-MRI imaging data and at least one selected biomarker is determined using DCS-MRI imaging data, optionally in combination with DCE-MRI imaging data; and 
   b. means for comparing the selected biomarkers with corresponding measurements for known malignant and benign tumors,   c. means for reporting or displaying the results of comparing the selected biomarkers with corresponding measurements for known malignant and benign tumors.   
     
     
         39 . The computer-based system of  claim 38 , wherein comparing the selected biomarkers comprise TTP, R2*-peakenh, and quantitative vp.