Intratumor mapping of intracellular water lifetime

Metabolic images of breast cancer?

Charles Jr Springer, Xin Li, Luminita (Alina) Tudorica, Karen Oh, Nicole Roy, Stephen (Steve) Chui, Arpana Naik, Megan L. Holtorf, Aneela Afzal, William Rooney, Wei Huang

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Shutter-speed pharmacokinetic analysis of dynamic-contrast-enhanced (DCE)-MRI data allows evaluation of equilibrium inter-compartmental water interchange kinetics. The process measured here - transcytolemmal water exchange - is characterized by the mean intracellular water molecule lifetime (τi). The τi biomarker is a true intensive property not accessible by any formulation of the tracer pharmacokinetic paradigm, which inherently assumes it is effectively zero when applied to DCE-MRI. We present population-averaged in vivo human breast whole tumor τi changes induced by therapy, along with those of other pharmacokinetic parameters. In responding patients, the DCE parameters change significantly after only one neoadjuvant chemotherapy cycle: while Ktrans (measuring mostly contrast agent (CA) extravasation) and kep (CA intravasation rate constant) decrease, τi increases. However, high-resolution, (1mm)2, parametric maps exhibit significant intratumor heterogeneity, which is lost by averaging. A typical 400ms τi value means a trans-membrane water cycling flux of 1013 H2O molecules s-1/cell for a 12μm diameter cell. Analyses of intratumor variations (and therapy-induced changes) of τi in combination with concomitant changes of ve (extracellular volume fraction) indicate that the former are dominated by alterations of the equilibrium cell membrane water permeability coefficient, PW, not of cell size. These can be interpreted in light of literature results showing that τi changes are dominated by a PW(active) component that reciprocally reflects the membrane driving P-type ATPase ion pump turnover. For mammalian cells, this is the Na+,K+-ATPase pump. These results promise the potential to discriminate metabolic and microenvironmental states of regions within tumors in vivo, and their changes with therapy.

Original languageEnglish (US)
Pages (from-to)760-773
Number of pages14
JournalNMR in Biomedicine
Volume27
Issue number7
DOIs
StatePublished - 2014

Fingerprint

Pharmacokinetics
Breast Neoplasms
Water
Magnetic resonance imaging
Contrast Media
Adenosine Triphosphatases
Tumors
Ion Pumps
Cell Membrane Permeability
Membranes
Molecules
Chemotherapy
Hydraulic conductivity
Interchanges
Biomarkers
Cell membranes
Cell Size
Rate constants
Volume fraction
Therapeutics

Keywords

  • Heterogeneity
  • Intratumor
  • Maps
  • Metabolic activity
  • Therapy

ASJC Scopus subject areas

  • Spectroscopy
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Medicine(all)

Cite this

Intratumor mapping of intracellular water lifetime : Metabolic images of breast cancer? / Springer, Charles Jr; Li, Xin; Tudorica, Luminita (Alina); Oh, Karen; Roy, Nicole; Chui, Stephen (Steve); Naik, Arpana; Holtorf, Megan L.; Afzal, Aneela; Rooney, William; Huang, Wei.

In: NMR in Biomedicine, Vol. 27, No. 7, 2014, p. 760-773.

Research output: Contribution to journalArticle

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