MRI of human tumor xenografts in vivo: Proton relaxation times and extracellular tumor volume

Jakobsen, Ingvil; Lyng, Heidi; Kaalhus, Olav; Rofstad, Einar K.

doi:10.1016/0730-725x(95)00019-d

Cited by 29 publications

(43 citation statements)

References 14 publications

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“…1B between the lesion and the healthyappearing breast tissue. It has been hypothesized that another source for the increase in T 1 in tumor tissue is the change in the ratios of free and bound water due to an increase in the extravascular extracellular volume fraction [43]. As ν e decreases, T 1 should decrease as well, and both parameters did decrease after treatment, although a significant correlation was not seen in the present data set.…”

Section: Discussioncontrasting

confidence: 54%

Integration of quantitative DCE-MRI and ADC mapping to monitor treatment response in human breast cancer: initial results

Yankeelov¹,

Lepage²,

Chakravarthy³

et al. 2007

Magnetic Resonance Imaging

284

266

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Purpose-The objective of this study was to assess changes in the water apparent diffusion coefficient (ADC) and in pharmacokinetic parameters obtained from the fast-exchange regime (FXR) modeling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) during neoadjuvant chemotherapy in breast cancer.Materials and Methods-Eleven patients with locally advanced breast cancer underwent MRI examination prior to and after chemotherapy but prior to surgery. A 1.5-T scanner was used to obtain T 1 , ADC and DCE-MRI data. DCE-MRI data were analyzed by the FXR model returning estimates of K trans (volume transfer constant), ν e (extravascular extracellular volume fraction) and τs i (average intracellular water lifetime). Histogram and correlation analyses assessed parameter changes posttreatment.Results-Significant ( P <.05) changes or trends towards significance ( P <.10) were seen in all parameters except τ i , although there was qualitative reduction in τ i values post-treatment. In particular, there was reduction ( P <.035) in voxels with K trans values in the range 0.2-0.5 min -1 and a decrease ( P <.05) in voxels with ADC values in the range 0.99×10 -3 to 1.35×10 -3 mm 2 /s. ADC and ν e were negatively correlated (r = -.60, P <.02). Parameters sensitive to water distribution and geometry (T 1 , ν e ,τs i and ADC) correlated with a multivariable linear regression model. Conclusion-The analysis presented here is sensitive to longitudinal changes in breast tumor status; K trans and ADC are most sensitive to these changes. Relationships between parameters provide information on water distribution and geometry in the tumor environment.

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Section: Discussioncontrasting

confidence: 54%

Integration of quantitative DCE-MRI and ADC mapping to monitor treatment response in human breast cancer: initial results

Yankeelov¹,

Lepage²,

Chakravarthy³

et al. 2007

Magnetic Resonance Imaging

284

266

View full text Add to dashboard Cite

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“…Consequently, addition of soluble proteins dose-dependently decreased T 1 (15). Studies of untreated human melanoma xenografts showed that tumor T 1 was correlated positively with extracellular tumor water content (16,(18)(19)(20) and proliferation (21), but negatively with necrosis (18,19). Theoretically, cell destruction would lead to the release of macromolecules and denatured proteins, as well as paramagnetic ions from damaged erythrocytes and thus reduce T 1 .…”

Section: Discussionmentioning

confidence: 99%

“…Earlier studies using a different method showed that the T 1 of experimental tumors was greater than in normal tissue and was considered to reflect predominantly the extracellular space (14)(15)(16)(17), with a larger interstitial compartment giving a longer (higher) T 1 . In untreated tumors, a low tumor T 1 has been correlated to increased necrosis (16,18), low water content (14)(15)(16)(17)(18)(19)(20), high levels of soluble protein (15), and low proliferation (21). Animals treated with chemotherapy or radiotherapy showed increases (22)(23)(24) and decreases (15,25) in tumor T 1 .…”

mentioning

confidence: 99%

Quantified Tumor T1 Is a Generic Early-Response Imaging Biomarker for Chemotherapy Reflecting Cell Viability

McSheehy

Weidensteiner

Cannet

et al. 2010

Clinical Cancer Research

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Purpose: Identification of a generic response biomarker by comparison of chemotherapeutics with different action mechanisms on several noninvasive biomarkers in experimental tumor models.Experimental Design: The spin-lattice relaxation time of water protons (T 1 ) was quantified using an inversion recovery-TrueFISP magnetic resonance imaging method in eight different experimental tumor models before and after treatment at several different time points with five different chemotherapeutics. Effects on T 1 were compared with other minimally invasive biomarkers including vascular parameters, apparent diffusion coefficient, and interstitial fluid pressure, and were correlated with efficacy at the endpoint and histologic parameters.Results: In all cases, successful chemotherapy significantly lowered tumor T 1 compared with vehicle and the fractional change in T 1 (ΔT 1 ) correlated with the eventual change in tumor size (range: r 2 = 0.21, P < 0.05 to r 2 = 0.73, P < 0.0001), except for models specifically resistant to that drug. In RIF-1 tumors, interstitial fluid pressure was decreased, but apparent diffusion coefficient and permeability increased in response to the microtubule stabilizer patupilone and 5-fluorouracil. Although ΔT 1 was small (maximum of −20%), the variability was very low (5%) compared with other magnetic resonance imaging methods (24-48%). Analyses ex vivo showed unchanged necrosis, increased apoptosis, and decreased %Ki67 and total choline, but only Ki67 and choline correlated with ΔT 1 . Correlation of Ki67 and ΔT 1 were observed in other models using patupilone, paclitaxel, a VEGF-R inhibitor, and the mammalian target of rapamycin inhibitor everolimus. Conclusions: These results suggest that a decrease in tumor T 1 reflects hypocellularity and is a generic marker of response. The speed and robustness of the method should facilitate its use in clinical trials. Clin Cancer Res; 16(1); 212-25. ©2010 AACR.

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“…Stromal-ECM of increasing collagen density was modeled computationally as 27,000-μm 3 cubes containing anisotropically oriented collagen fibers. The number of fibers were chosen to achieve collagen volume fractions (8.72-87.20%), reflective of conditions found within tumors (33,34). Diffusion distance for 500 AuNP replicates was tracked for 5,000 discrete steps at 1-s intervals.…”

Section: Computational Modeling Of Nanoparticle Diffusion Through Porousmentioning

confidence: 99%

Tailoring nanoparticle designs to target cancer based on tumor pathophysiology

Sykes

Dai

Sarsons

et al. 2016

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

243

163

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Nanoparticles can provide significant improvements in the diagnosis and treatment of cancer. How nanoparticle size, shape, and surface chemistry can affect their accumulation, retention, and penetration in tumors remains heavily investigated, because such findings provide guiding principles for engineering optimal nanosystems for tumor targeting. Currently, the experimental focus has been on particle design and not the biological system. Here, we varied tumor volume to determine whether cancer pathophysiology can influence tumor accumulation and penetration of different sized nanoparticles. Monte Carlo simulations were also used to model the process of nanoparticle accumulation. We discovered that changes in pathophysiology associated with tumor volume can selectively change tumor uptake of nanoparticles of varying size. We further determine that nanoparticle retention within tumors depends on the frequency of interaction of particles with the perivascular extracellular matrix for smaller nanoparticles, whereas transport of larger nanomaterials is dominated by Brownian motion. These results reveal that nanoparticles can potentially be personalized according to a patient's disease state to achieve optimal diagnostic and therapeutic outcomes.cancer | nanoparticles | targeting | nano-bio interactions | tumor

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MRI of human tumor xenografts in vivo: Proton relaxation times and extracellular tumor volume

Cited by 29 publications

References 14 publications

Integration of quantitative DCE-MRI and ADC mapping to monitor treatment response in human breast cancer: initial results

Integration of quantitative DCE-MRI and ADC mapping to monitor treatment response in human breast cancer: initial results

Quantified Tumor T1 Is a Generic Early-Response Imaging Biomarker for Chemotherapy Reflecting Cell Viability

Tailoring nanoparticle designs to target cancer based on tumor pathophysiology

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