Impact of transcytolemmal water exchange on estimates of tissue microstructural properties derived from diffusion MRI

Li, Hua; Jiang, Xiaoyu; Xie, Jingping; Gore, John C.; Xu, Junzhong

doi:10.1002/mrm.26309

Cited by 52 publications

(77 citation statements)

References 52 publications

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“…However, recent studies have found the accuracy of the measurements of f in are significantly affected by k in themselves. A recent study [40] reports that f in values obtained from either quantitative PGSE (pulsed gradient spin echo) [41] or OGSE (oscillating gradient spin echo) [42, 43] diffusion sequences are significantly underestimated due to transcytolemmal water exchange, while fitted cell size values are less influenced. Another study found out that “DCE-MRI is not a reliable biomarker of extracellular space for a range of physiological conditions” confirmed with histology analysis [44].…”

Section: Discussionmentioning

confidence: 99%

Evaluation and comparison of diffusion MR methods for measuring apparent transcytolemmal water exchange rate constant

Tian

Jiang

et al. 2017

Journal of Magnetic Resonance

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Two diffusion-based approaches, CG (constant gradient) and FEXI (filtered exchange imaging) methods, have been previously proposed for measuring transcytolemmal water exchange rate constant kin, but their accuracy and feasibility have not been comprehensively evaluated and compared. In this work, both computer simulations and cell experiments in vitro were performed to evaluate these two methods. Simulations were done with different cell diameters (5, 10, 20 µm), a broad range of kin values (0.02 – 30 s−1) and different SNR’s, and simulated kin’s were directly compared with the ground truth values. Human leukemia K562 cells were cultured and treated with saponin to selectively change cell transmembrane permeability. The agreement between measured kin’s of both methods was also evaluated. The results suggest that, without noise, the CG method provides reasonably accurate estimation of kin especially when it is smaller than 10 s−1, which is in the typical physiological range of many biological tissues. However, although the FEXI method overestimates kin even with corrections for the effects of extracellular water fraction, it provides reasonable estimates with practical SNR’s and more importantly, the fitted apparent exchange rate AXR showed approximately linear dependence on the ground truth kin. In conclusion, either CG or FEXI method provides a sensitive means to characterize the variations in transcytolemmal water exchange rate constant kin, although the accuracy and specificity is usually compromised. The non-imaging CG method provides more accurate estimation of kin, but limited to large volume-of-interest. Although the accuracy of FEXI is compromised with extracellular volume fraction, it is capable of spatially mapping kin in practice.

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Section: Discussionmentioning

confidence: 99%

Evaluation and comparison of diffusion MR methods for measuring apparent transcytolemmal water exchange rate constant

Tian

Jiang

et al. 2017

Journal of Magnetic Resonance

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“…Exchange of water across the sphere wall is another unmodeled effect that may contribute to bias in R and f i . As longer diffusion times are expected to increase sensitivity to exchange, it may be hypothesized that, depending on the rate of exchange, excluding the longest diffusion time data from the fitting would reduce such sensitivity and therefore improve the accuracy of R .…”

Section: Discussionmentioning

confidence: 99%

A biomimetic tumor tissue phantom for validating diffusion‐weighted MRI measurements

McHugh

Zhou

Wimpenny

et al. 2017

Magnetic Resonance in Med

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PurposeTo develop a biomimetic tumor tissue phantom which more closely reflects water diffusion in biological tissue than previously used phantoms, and to evaluate the stability of the phantom and its potential as a tool for validating diffusion‐weighted (DW) MRI measurements.MethodsCoaxial‐electrospraying was used to generate micron‐sized hollow polymer spheres, which mimic cells. The bulk structure was immersed in water, providing a DW‐MRI phantom whose apparent diffusion coefficient (ADC) and microstructural properties were evaluated over a period of 10 months. Independent characterization of the phantom's microstructure was performed using scanning electron microscopy (SEM). The repeatability of the construction process was investigated by generating a second phantom, which underwent high resolution synchrotron‐CT as well as SEM and MR scans.ResultsADC values were stable (coefficients of variation (CoVs) < 5%), and varied with diffusion time, with average values of 1.44 ± 0.03 µm2/ms (Δ = 12 ms) and 1.20 ± 0.05 µm2/ms (Δ = 45 ms). Microstructural parameters showed greater variability (CoVs up to 13%), with evidence of bias in sphere size estimates. Similar trends were observed in the second phantom.ConclusionA novel biomimetic phantom has been developed and shown to be stable over 10 months. It is envisaged that such phantoms will be used for further investigation of microstructural models relevant to characterizing tumor tissue, and may also find application in evaluating acquisition protocols and comparing DW‐MRI‐derived biomarkers obtained from different scanners at different sites. Magn Reson Med 80:147–158, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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“…The measured DWI signal S is shown by Equation :

S = v_{italicin} \cdot S_{italicin} + false(1 - v_{in} false) \cdot S_{italicex}

where S in , and S ex are the signal magnitudes per volume from the intra‐ and extracellular spaces, respectively, and v in is intracellular water fraction. Note that water exchange between intra‐ and extracellular spaces is ignored, but does not affect the estimation of mean cancer cell size, although it may bias the estimation of cell density …”

Section: Methodsmentioning

confidence: 99%

“…All MRI measurements of cells in vitro were performed on a Varian/Agilent 4.7T MRI spectrometer (Agilent Technologies, Santa Clara, CA) similar to the approach described previously . A 2‐mm‐thick slice crossing the center of each cell pellet was imaged with a field of view (FOV) 16 × 16 mm and a matrix size 64 × 64, yielding a spatial resolution of 250 μm.…”

Section: Methodsmentioning

confidence: 99%

Magnetic resonance imaging of mean cell size in human breast tumors

Jiang

et al. 2019

Magnetic Resonance in Med

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Purpose Cell size is a fundamental characteristic of all tissues, and changes in cell size in cancer reflect tumor status and response to treatments, such as apoptosis and cell‐cycle arrest. Unfortunately, cell size can currently be obtained only by pathological evaluation of tumor tissue samples obtained invasively. Previous imaging approaches are limited to preclinical MRI scanners or require relatively long acquisition times that are impractical for clinical imaging. There is a need to develop cell‐size imaging for clinical applications. Methods We propose a clinically feasible IMPULSED (imaging microstructural parameters using limited spectrally edited diffusion) approach that can characterize mean cell sizes in solid tumors. We report the use of a combination of pulse sequences, using different gradient waveforms implemented on clinical MRI scanners and analytical equations based on these waveforms to analyze diffusion‐weighted MRI signals and derive specific microstructural parameters such as cell size. We also describe comprehensive validations of this approach using computer simulations, cell experiments in vitro, and animal experiments in vivo and demonstrate applications in preoperative breast cancer patients. Results With fast acquisitions (~7 minutes), IMPULSED can provide high‐resolution (1.3 mm in‐plane) mapping of mean cell size of human tumors in vivo on clinical 3T MRI scanners. All validations suggest that IMPULSED provides accurate and reliable measurements of mean cell size. Conclusion The proposed IMPULSED method can assess cell‐size variations in tumors of breast cancer patients, which may have the potential to assess early response to neoadjuvant therapy.

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Impact of transcytolemmal water exchange on estimates of tissue microstructural properties derived from diffusion MRI

Cited by 52 publications

References 52 publications

Evaluation and comparison of diffusion MR methods for measuring apparent transcytolemmal water exchange rate constant

Evaluation and comparison of diffusion MR methods for measuring apparent transcytolemmal water exchange rate constant

A biomimetic tumor tissue phantom for validating diffusion‐weighted MRI measurements

Magnetic resonance imaging of mean cell size in human breast tumors

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