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

Abstract

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 (tau(i)) 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 tau(i) 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: K(trans), the vascular wall CR transfer rate constant, and v(e), 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 K(trans) and v(e) magnitudes on the CR dose. These parameters should be CR dose-independent. The most parsimonious analysis allowing for realistic tau(i) 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 K(trans). 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 K(trans), v(e), and tau(i) magnitudes, by comparison with results of previous careful rat leg studies not possible for human subjects.

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

“…These images were acquired with adipose -1 H 2 C-suppression (institutional protocol required). In contrast to those (13,14) obtained with no fat suppression, these darker images show glandular regions brighter than fatty tissues. (Fig.…”

“…We also used the FXR-and SXR-allowed (FXR-a and SXR-a) versions of the first-generation ShutterSpeed Model (SSM1), BOLus Enhanced Relaxation Overview (BOLERO) (8,11). In the SM analyses, the parameters varied are K trans and v e , while the i value is (implicitly) zero (11,13,14).…”

“…In some SSM analyses, i is also varied. The complete 9-parameter set has been tabulated (14) and the constant values of the other parameters have been reported (13,14).…”

“…The model has the constraints that i is vanishingly small (the FXL) and that the transverse relaxation factor [exp(ϪTE⅐R 2 ‫ء‬ )] ϭ 1. The dashed curve shows the characteristic undershoot at the beginning, followed by overshoot and then undershoot during the washout (11,13,14). The K trans and v e parameter values from this fitting are listed in Table 1.…”

“…This corollary is not valid (2,6), and its assumption can effectively short circuit MRI determination of CR compartmentalization (2, 7)-the pharmacokinetic essence. In a series of papers (2,5,6,(8)(9)(10)(11)(12)(13)(14)(15)(16), we have examined the significance of this implication. We refer to models incorporating equilibrium exchange effects in the pharmacokinetic derivation as belonging to the shutter-speed model (SSM) family.…”