Dynamic NMR effects in breast cancer dynamic-contrast-enhanced MRI

The passage of a vascular-injected paramagnetic contrast reagent (CR) bolus through a region-of-interest affects tissue 1H2O relaxation and thus MR image intensity. For longitudinal relaxation [R1 ≡ (T1)−1], the CR must have transient molecular interactions with water. Because the CR and water molecules are never uniformly distributed in the histological-scale tissue compartments, the kinetics of equilibrium water compartmental interchange are competitive. In particular, the condition of the equilibrium trans cytolemmal water exchange NMR system sorties through different domains as the interstitial CR concentration, [CRo], waxes and wanes. Before CR, the system is in the fast-exchange-limit (FXL). Very soon after CRo arrival, it enters the fast-exchange-regime (FXR). Near maximal [CRo], the system could enter even the slow-exchange-regime (SXR). These conditions are defined herein, and a comprehensive description of how they affect quantitative pharmacokinetic analyses is presented. Data are analyzed from a population of 22 patients initially screened suspicious for breast cancer. After participating in our study, the subjects underwent biopsy/pathology procedures and only 7 (32%) were found to have malignancies. The transient departure from FXL to FXR (and apparently not SXR) is significant in only the malignant tumors, presumably because of angiogenic capillary leakiness. Thus, if accepted, this analysis would have prevented the 68% of the biopsies that proved benign.

[1]  C. Springer,et al.  Using flow relaxography to elucidate flow relaxivity. , 1999, Journal of magnetic resonance.

[2]  Jaladhar Neelavalli,et al.  Susceptibility‐weighted imaging to visualize blood products and improve tumor contrast in the study of brain masses , 2006, Journal of magnetic resonance imaging : JMRI.

[3]  Xin Li,et al.  A unified magnetic resonance imaging pharmacokinetic theory: Intravascular and extracellular contrast reagents , 2005, Magnetic resonance in medicine.

[4]  K. Uğurbil,et al.  Magnetic field and tissue dependencies of human brain longitudinal 1H2O relaxation in vivo , 2007, Magnetic resonance in medicine.

[5]  D. Woessner,et al.  Nuclear Transfer Effects in Nuclear Magnetic Resonance Pulse Experiments , 1961 .

[6]  C. Patlak,et al.  Susceptibility changes following bolus injections , 1993, Magnetic resonance in medicine.

[7]  Enzo Terreno,et al.  Effect of the intracellular localization of a Gd‐based imaging probe on the relaxation enhancement of water protons , 2006, Magnetic resonance in medicine.

[8]  P. Gullino Extracellular Compartments of Solid Tumors , 1975 .

[9]  K. Miller,et al.  Antiangiogenic Agents in Breast Cancer , 2007, Cancer investigation.

[10]  R. Jain Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy , 2005, Science.

[11]  P S Tofts,et al.  Quantitative Analysis of Dynamic Gd‐DTPA Enhancement in Breast Tumors Using a Permeability Model , 1995, Magnetic resonance in medicine.

[12]  R M Weisskoff,et al.  Water diffusion and exchange as they influence contrast enhancement , 1997, Journal of magnetic resonance imaging : JMRI.

[13]  Xin Li,et al.  Equilibrium transcytolemmal water‐exchange kinetics in skeletal muscle in vivo , 1999, Magnetic resonance in medicine.

[14]  M. Knopp,et al.  Estimating kinetic parameters from dynamic contrast‐enhanced t1‐weighted MRI of a diffusable tracer: Standardized quantities and symbols , 1999, Journal of magnetic resonance imaging : JMRI.

[15]  D. Look,et al.  Time Saving in Measurement of NMR and EPR Relaxation Times , 1970 .

[16]  Xin Li,et al.  The Evaluation of Esophageal Adenocarcinoma Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging , 2007, Journal of Gastrointestinal Surgery.

[17]  J. Balschi,et al.  Magnetic field dependence of 23Na NMR spectra of rat skeletal muscle infused with shift reagent in Vivo , 1989 .

[18]  Klaas Dijkstra,et al.  A single-scan fourier transform method for measuring spin-lattice relaxation times , 1976 .

[19]  R. Bryant The NMR time scale , 1983 .

[20]  J. Neil,et al.  Intracellular water‐specific MR of microbead‐adherent cells: the HeLa cell intracellular water exchange lifetime , 2008, NMR in biomedicine.

[21]  L D Buadu,et al.  Breast lesions: correlation of contrast medium enhancement patterns on MR images with histopathologic findings and tumor angiogenesis. , 1996, Radiology.

[22]  Wei Huang,et al.  Evidence for shutter‐speed variation in CR bolus‐tracking studies of human pathology , 2005, NMR in biomedicine.

[23]  E. Preston,et al.  Diffusion into rat brain of contrast and shift reagents for magnetic resonance imaging and spectroscopy , 1993, NMR in biomedicine.

[24]  W. Rooney,et al.  Determination of the MRI contrast agent concentration time course in vivo following bolus injection: Effect of equilibrium transcytolemmal water exchange , 2000, Magnetic resonance in medicine.

[25]  Scott Fields,et al.  Mapping pathophysiological features of breast tumors by MRI at high spatial resolution , 1997, Nature Medicine.

[26]  Charles S Springer,et al.  Equilibrium water exchange between the intra‐ and extracellular spaces of mammalian brain , 2003, Magnetic resonance in medicine.

[27]  M. Bruvold,et al.  Analyzing equilibrium water exchange between myocardial tissue compartments using dynamical two‐dimensional correlation experiments combined with manganese‐enhanced relaxography , 2007, Magnetic resonance in medicine.

[28]  G. Glover,et al.  Breast disease: dynamic spiral MR imaging. , 1998, Radiology.

[29]  C. Springer,et al.  Relaxographic imaging. , 1994, Journal of magnetic resonance. Series B.

[30]  Thomas E Yankeelov,et al.  Integration of quantitative DCE-MRI and ADC mapping to monitor treatment response in human breast cancer: initial results. , 2007, Magnetic resonance imaging.

[31]  Ronald G. Blasberg,et al.  Transport of α-Aminoisobutyric Acid across Brain Capillary and Cellular Membranes , 1983 .

[32]  Rong Zhou,et al.  Simultaneous measurement of arterial input function and tumor pharmacokinetics in mice by dynamic contrast enhanced imaging: Effects of transcytolemmal water exchange , 2004, Magnetic resonance in medicine.

[33]  Harry Quon,et al.  Transcytolemmal water exchange in pharmacokinetic analysis of dynamic contrast‐enhanced MRI data in squamous cell carcinoma of the head and neck , 2007, Journal of magnetic resonance imaging : JMRI.

[34]  R. Spencer,et al.  Measurement of Spin-Lattice Relaxation Times in Systems Undergoing Chemical Exchange , 1994 .

[35]  K. Schmainda,et al.  Water exchange and inflow affect the accuracy of T1‐GRE blood volume measurements: Implications for the evaluation of tumor angiogenesis , 2002, Magnetic resonance in medicine.

[36]  B. Hills,et al.  NMR Studies of Membrane Transport , 1989 .

[37]  C. S. Springer,et al.  Physicochemical Principles Influencing Magnetopharmaceuticals , 1994 .

[38]  Charles Randall. House,et al.  Water transport in cells and tissues , 1974 .

[39]  Michael Jerosch-Herold,et al.  First‐pass dynamic contrast‐enhanced MRI with extravasating contrast reagent: evidence for human myocardial capillary recruitment in adenosine‐induced hyperemia , 2009, NMR in biomedicine.

[40]  Thomas E Yankeelov,et al.  Incorporating the effects of transcytolemmal water exchange in a reference region model for DCE‐MRI analysis: Theory, simulations, and experimental results , 2008, Magnetic resonance in medicine.

[41]  W. Rooney,et al.  The effects of equilibrium transcytolemmal water exchange on the determination of contrast reagent concentration in vivo , 2002 .

[42]  Wei Huang,et al.  Shutter‐speed analysis of contrast reagent bolus‐tracking data: Preliminary observations in benign and malignant breast disease , 2005, Magnetic resonance in medicine.

[43]  Thomas E Yankeelov,et al.  Variation of the relaxographic “shutter‐speed” for transcytolemmal water exchange affects the CR bolus‐tracking curve shape , 2003, Magnetic resonance in medicine.

[44]  J. Balschi,et al.  31P and 23Na NMR spectroscopy of normal and ischemic rat skeletal muscle. Use of a shift reagent in vivo , 1990, NMR in biomedicine.