Evidence for shutter-speed variation in CR bolus-tracking studies of human pathology

Thomas E. Yankeelov, William D. Rooney, Wei Huang, Jonathan P. Dyke, Xin Li, Alina Tudorica, Jing Huei Lee, Jason A. Koutcher, Charles S. Springer

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


The standard pharmacokinetic model for the analysis of MRI contrast reagent (CR) bolus-tracking (B-T) data assumes that the mean intracellular water molecule lifetime (τi) is effectively zero. This assertion is inconsistent with a considerable body of physiological measurements. Furthermore, theory and simulation show the B-T time-course shape to be very sensitive to the τi magnitude in the physiological range (hundreds of milliseconds to several seconds). Consequently, this standard model aspect can cause significant underestimations (factors of 2 or 3) of the two parameters usually determined: Ktrans, the vascular wall CR transfer rate constant, and ve, the CR distribution volume (the extracellular, extravascular space fraction). Analyses of animal model data confirmed two predicted behaviors indicative of this standard model inadequacy: (1) a specific temporal pattern for the mismatch between the best-fitted curve and data; and (2) an inverse dependence of the curve's Ktrans and ve magnitudes on the CR dose. These parameters should be CR, dose-independent. The most parsimonious analysis allowing for realistic τi values is the 'shutter-speed' model. Its application to the experimental animal data essentially eliminated the two standard model signature inadequacies. This paper reports the first survey for the extent of this 'shutter-speed effect' in human data. Retrospective analyses are made of clinical data chosen from a range of pathology (the active multiple sclerosis lesion, the invasive ductal carcinoma breast tumor, and osteosarcoma in the leg) that provides a wide variation, particularly of Ktrans. The signature temporal mismatch of the standard model is observed in all cases, and is essentially eliminated by use of the shutter-speed model. Pixel-by-pixel maps show that parameter values from the shutter-speed analysis are increased by more than a factor of 3 for some lesion regions. This endows the lesions with very high contrast, and reveals heterogeneities that are often not seen in the standard model maps. Normal muscle regions in the leg allow validation of the shutter-speed model Ktrans, ve, and τ i magnitudes, by comparison with results of previous careful rat leg studies not possible for human subjects.

Original languageEnglish (US)
Pages (from-to)173-185
Number of pages13
JournalNMR in biomedicine
Issue number3
StatePublished - May 2005


  • Bolus-tracking
  • Contrast reagent
  • Invasive ductal carcinoma
  • Multiple sclerosis
  • Osteosarcoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Spectroscopy


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