Simultaneous measurement of arterial input function and tumor pharmacokinetics in mice by dynamic contrast enhanced imaging: Effects of transcytolemmal water exchange

Zhou, Rong; Pickup, Stephen; Yankeelov, Thomas E.; Springer, Charles S.; Glickson, Jerry D.

doi:10.1002/mrm.20143

Cited by 84 publications

(130 citation statements)

References 32 publications

(64 reference statements)

Supporting

Mentioning

119

Contrasting

Order By: Relevance

“…This signature has been experimentally observed for fittings of rodent data conducted by ourselves (7,12) and others (13,14). The second signature, K trans and v e underestimations increasing with CR dose (7), has also been observed in mouse tumor model data (12). This second test is harder to accomplish with humans, but the first signature has been observed in initial studies of a human MS lesion, a breast invasive ductal carcinoma (IDC), and an osteosarcoma of the leg (15).…”

supporting

confidence: 57%

“…One of these is a specific temporal mismatch of the bestfitted standard model curve and the B-T data shape: the model lags behind during the tissue CR wash-in, then oscillates during wash-out, initially overshooting and later undershooting (7). This signature has been experimentally observed for fittings of rodent data conducted by ourselves (7,12) and others (13,14). The second signature, K trans and v e underestimations increasing with CR dose (7), has also been observed in mouse tumor model data (12).…”

mentioning

confidence: 83%

“…The metaphor of the relaxographic NMR shutter-speed, ͉ r 1o [CR o (7). The use of this shutter-speed model with the rodent tumor (7,12) and human pathology (15) data essentially eliminates the two signature inadequacies of the standard model. Furthermore, preliminary application of this model to in vivo B-T data from rectus femoris muscle in the human leg (15) yielded a i value (1.3 s) in excellent agreement with that (1.1 s) reported for a rat leg muscle ROI from a non-B-T study involving programmed-infusion CR titrations averaged for a number of animals (8)-a somewhat more controlled and comprehensive approach not available for human subjects.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Shutter‐speed analysis of contrast reagent bolus‐tracking data: Preliminary observations in benign and malignant breast disease

Huang

Yankeelov

et al. 2005

Magnetic Resonance in Med

Self Cite

103

View full text Add to dashboard Cite

The standard pharmacokinetic model applied to contrast reagent (CR) bolus-tracking (B-T) MRI (dynamic-contrast-enhanced) data makes the intrinsic assumption that equilibrium transcytolemmal water molecule exchange is effectively infinitely fast. Theory and simulation have suggested that this assumption can lead to significant errors. Recent analyses of animal model experimental data have confirmed two predicted signature inadequacies: a specific temporal mismatch with the B-T time-course and a CR dose-dependent underestimation of model parameters. The most parsimonious adjustment to account for this aspect leads to the "shutter-speed" pharmacokinetic model. Application of the latter to the animal model data mostly eliminates the two signature inadequacies. Here, the standard and shutter-speed models are applied to B-T data obtained from routine human breast examinations. The MRI contrast reagent (CR) bolus-tracking (B-T) (also called dynamic-contrast-enhanced)] method holds great promise for quantitative in vivo evaluation of vascular properties under many different pathophysiological conditions (1). An area that has seen considerable such activity is breast disease (2-5). The many pharmacokinetic models applied to CR B-T data can be divided into two families; one in which the CR and H 2 O are assumed uniformly distributed within each compartment entered ["well-mixed," e.g., (1)] and one in which they are not ["heterogeneous," surveyed in (6)]. For a given number of compartments, the former models have fewer variable parameters: heterogeneous distributions require geometric quantities. Of course, for a given model family, the number of parameters increases with the number of compartments. Even the simplest well-mixed model, which considers only two compartments for CR (1), has seven potential parameters (listed below) (7). Most fittings employ versions in which only two of these, K trans [a pseudo-firstorder rate constant for CR transfer between blood plasma and extracellular, extravascular space (EES)] and the CR distribution volume, equated to v e (the EES volume fraction)-or combinations thereof-are varied (1). However, we have recently shown that this "standard model" embeds the intrinsic assumption that an important eighth parameter, the mean intracellular water lifetime ( i ), is effectively zero: that is, the equilibrium transcytolemmal water exchange system is constrained to the fast-exchangelimit (FXL) (7). This is inconsistent with cytolemmal water permeability coefficient (P) values (measured over many years), which when combined with mean cell sizes allow calculations of i [ϭ r/(3P), for a sphere of radius r]: this is reviewed in Ref. (8). These estimates, along with recent independent measurements (8 -11), yield i values that for almost all cells (except erythrocytes) range from hundreds of milliseconds to several seconds. Such magnitudes have significant effects on the two-compartment model B-T time-course amplitude and shape, causing data fitting with the standard model to underestimate the K tran...

show abstract

supporting

confidence: 57%

mentioning

confidence: 83%

mentioning

confidence: 99%

See 1 more Smart Citation

Shutter‐speed analysis of contrast reagent bolus‐tracking data: Preliminary observations in benign and malignant breast disease

Huang

Yankeelov

et al. 2005

Magnetic Resonance in Med

Self Cite

103

View full text Add to dashboard Cite

show abstract

“…This apparent discrepancy regarding the efficacy of PK parameters may be due to the relatively small number of cases included in various studies, or the wide variety of DCE-MRI acquisition and PK analysis techniques used. Intra-tumour vascular heterogeneity might also be significant in some breast cancers (Hayes et al, 2002), leading to the possible breakdown of PK model assumptions such as the fast exchange limit within better-perfused regions (usually located at the tumour rim) (Zhou et al, 2004;Li et al, 2005). This could present a complicating factor in obtaining reliable results, an issue not addressed in this study, which utilised a whole ROI approach so as to minimise the effects of intra-scan patient motion.…”

Section: Discussionmentioning

confidence: 98%

Neoadjuvant chemotherapy in breast cancer: early response prediction with quantitative MR imaging and spectroscopy

et al. 2006

View full text Add to dashboard Cite

A prospective study was undertaken in women undergoing neoadjuvant chemotherapy for locally advanced breast cancer in order to determine the ability of quantitative magnetic resonance imaging (MRI) and proton spectroscopy (MRS) to predict ultimate tumour response (percentage decrease in volume) or to detect early response. Magnetic resonance imaging and MRS were carried out before treatment and after the second of six treatment cycles. Pharmacokinetic parameters were derived from T 1 -weighted dynamic contrast-enhanced MRI, water apparent diffusion coefficient (ADC) was measured, and tissue water : fat peak area ratios and water T 2 were measured using unsuppressed one-dimensional proton spectroscopic imaging (30 and 135 ms echo times). Pharmacokinetic parameters and ADC did not detect early response; however, early changes in water : fat ratios and water T 2 (after cycle two) demonstrated substantial prognostic efficacy. Larger decreases in water T 2 accurately predicted final volume response in 69% of cases (11/16) while maintaining 100% specificity and positive predictive value. Small/absent decreases in water : fat ratios accurately predicted final volume non-response in 50% of cases (3/6) while maintaining 100% sensitivity and negative predictive value. This level of accuracy might permit clinical application where early, accurate prediction of non-response would permit an early change to second-line treatment, thus sparing patients unnecessary toxicity, psychological morbidity and delay of initiation of effective treatment.

show abstract

“…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.…”

Section: Dynamic Nuclear Magnetic Resonance (Dnmr)mentioning

confidence: 99%

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

Huang

Morris

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

147

View full text Add to dashboard Cite

The passage of a vascular-injected paramagnetic contrast reagent (CR) bolus through a region-of-interest affects tissue 1 H2O relaxation and thus MR image intensity. For longitudinal relaxation [R1 ϵ (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 transcytolemmal 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 slowexchange-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.water exchange ͉ screening ͉ shutter speed

show abstract

Simultaneous measurement of arterial input function and tumor pharmacokinetics in mice by dynamic contrast enhanced imaging: Effects of transcytolemmal water exchange

Cited by 84 publications

References 32 publications

Shutter‐speed analysis of contrast reagent bolus‐tracking data: Preliminary observations in benign and malignant breast disease

Shutter‐speed analysis of contrast reagent bolus‐tracking data: Preliminary observations in benign and malignant breast disease

Neoadjuvant chemotherapy in breast cancer: early response prediction with quantitative MR imaging and spectroscopy

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

Contact Info

Product

Resources

About