Relationship Between Hydration and Proton Nuclear Magnetic Resonance Relaxation Times in Tissues of Tumor-Bearing and Non-Tumor-Bearing Mice: Implications for Cancer Detection
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Hazlewood, Carlton F.; Cleveland, G.; Medina, Daniel

doi:10.1093/jnci/52.6.1849

Cited by 90 publications

(8 citation statements)

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“…These data have been interpreted by some investigators as being consistent with the concept of "ordering" of the intracellular water (i.e. shorter relaxation times imply longer correlation times and thus indicate a more ordered state) (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Other investigators have proposed alternative explanations of the change in these parameters (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43).…”

Section: Introductionsupporting

confidence: 55%

Nuclear magnetic resonance measurement of skeletal muscle: anisotrophy of the diffusion coefficient of the intracellular water

Cleveland¹,

Chang²,

Hazlewood³

et al. 1976

Biophysical Journal

222

134

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The anisotropy of the spin-diffusion coefficient Ds of water protons in skeletal muscle has been studied by pulsed NMR methods. The mid-portion of the tibialis anterior muscle of mature male rats was placed in a special sample holder by means of which the muscle fiber orientation theta relative to the diffusion direction could be varied over the range 0 degrees less than or equal to theta less than or equal to 90 degrees. The value of Ds(theta) was determined for theta = 0 degrees, 45 degrees, and 90 degrees. The measured anisotropy Ds(0)/Ds(90) was 1.39, and the value of Ds(0) was 1.39 X 10(-5) cm2/s. These results are interpreted within the framework of a model calculation in which the diffusion equation is solved for a regular hexagonal network similar to the actin-myosin filament network. The large anisotropy, and the large reduction in the value of Ds measured parallel to the filament axes lead to two major conclusions: (a) interpretations in which the reduction in Ds is ascribed to the effect of geometrical obstructions on the diffusion of "free" water are ruled out; and, (b) there is a large fraction of the cellular water associated with the proteins in such a way that its diffusion coefficient is substantially reduced.

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Section: Introductionsupporting

confidence: 55%

Nuclear magnetic resonance measurement of skeletal muscle: anisotrophy of the diffusion coefficient of the intracellular water

Cleveland¹,

Chang²,

Hazlewood³

et al. 1976

Biophysical Journal

222

134

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“…Damadian (10) first documented distinct differences in proton relaxation rates between normal and cancerous tissues as early as 1971, which was also confirmed by various groups in the subsequent years (11–15). Clinical diagnosis and monitoring of brain tumors with MRI, however, remains reliant on the use of T 1 or T 2 “weighted” images, which express qualitative changes in the MR signal.…”

Section: Introductionmentioning

confidence: 70%

Quantification of Nonenhancing Tumor Burden in Gliomas Using Effective T2 Maps Derived from Dual-Echo Turbo Spin-Echo MRI

Ellingson

Lai

Nguyen

et al. 2015

Clinical Cancer Research

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Purpose Evaluation of nonenhancing tumor (NET) burden is an important, yet challenging part of brain tumor response assessment. The current study focuses on using dual echo turbo spin echo MRI as a means of quickly estimating tissue T2, which can be used to objectively define NET burden. Experimental Design A series of experiments were performed to establish the use of T2 maps for defining NET burden. First, variation in T2 was determined using ACR water phantoms in 16 scanners evaluated over 3 years. Next, sensitivity and specificity of T2 maps for delineating NET from other tissues was examined. Then, T2-defined NET was used to predict survival in separate subsets of glioblastoma patients treated with radiation therapy, concurrent radiation and chemotherapy, or bevacizumab at recurrence. Results Variability in T2 in the ACR phantom was 3-5%. In training data, ROC analysis suggested that 125ms < T2 < 250ms could delineate NET with a sensitivity >90% and specificity >65%. Using this criterion, NET burden after completion of radiation therapy alone, or concurrent radiation therapy and chemotherapy, was shown to be predictive of survival (Cox, P<0.05), and the change in NET volume before and after bevacizumab therapy in recurrent glioblastoma was also a predictive of survival (P<0.05). Conclusions T2 maps using dual echo data are feasible, stable, and can be used to objectively define NET burden for use in brain tumor characterization, prognosis, and response assessment. The use of effective T2 maps for defining NET burden should be validated in a randomized clinical trial.

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“…Chronically hypoxic cells arise as a result of limited oxygen diffusion and are thus often found adjacent to necrosis (Chapman 1991) . Moreover, fractional tumour water content has been shown to be a predominant factor influencing the values of proton T and T2 of tumours (Damadian 1971, Hazlewood et al . 1974, Inch et al .…”

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confidence: 99%

Magnetic Resonance Imaging of Human Melanoma Xenograftsin Vivo: Proton Spin—lattice and Spin—spin Relaxation Times Versus Fractional Tumour Water Content and Fraction of Necrotic Tumour Tissue

Rofstad

Steinsland

Kaalhus

et al. 1994

International Journal of Radiation Biology

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Proton nuclear magnetic resonance (1H-nmr) imaging is used routinely in clinical oncology to provide macroscopic anatomical information, whereas its potential to provide physiological information about tumours is not well explored. To evaluate the potential usefulness of 1H-nmr imaging in the prediction of tumour treatment resistance caused by unfavourable microenvironmental conditions, possible correlations between proton spin-lattice and spin-spin relaxation times (T1 and T2) and physiological parameters of the tumour microenvironment were investigated. Tumours from six human melanoma xenograft lines were included in the study. 1H-nmr imaging was performed at 1.5 T using spin-echo pulse sequences. T1- and T2-distributions were generated from the images. Fractional tumour water content and the fraction of necrotic tumour tissue were measured immediately after 1H-nmr imaging. Significant correlations across tumour lines were found for T1 and T2 versus fractional tumour water content (p < 0.001) as well as for T1 and T2 versus fraction of necrotic tumour tissue (p < 0.05). Tumours with high fractional water contents had high values of T1 and T2, probably caused by free water in the tumour interstitium. Fractional water content is correlated to interstitial fluid pressure in tumours, high interstitial fluid pressure being indicative of high vascular resistance. Tumours with high fractional water contents are thus expected to show regions with radiobiologically hypoxic cells as well as poor intravascular and interstitial transport of many therapeutic agents. T1 and T2 decreased with increasing fraction of necrotic tumour tissue, perhaps because complexed paramagnetic ions were released during development of necrosis. Viable tumour cells adjacent to necrotic regions are usually chronically hypoxic. Tumours with high fractions of necrotic tissue are thus expected to contain significant proportions of radiobiologically hypoxic cells. Consequently, quantitative 1H-nmr imaging has the potential to be developed as an efficient clinical tool in prediction of tumour treatment resistance caused by hypoxia and/or transport barriers for therapeutic agents. However, much work remains to be done before this potential can be adequately evaluated. One problem is that high fractional tumour water contents result in longer T1 and T2 whereas high fractions of necrotic tumour tissue result in shorter T1 and T2; i.e. the two parameters which are indicative of treatment resistance contribute in opposite directions. Another problem is that the correlations for T1 and T2 versus fraction of necrotic tumour tissue are not particularly strong.

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Relationship Between Hydration and Proton Nuclear Magnetic Resonance Relaxation Times in Tissues of Tumor-Bearing and Non-Tumor-Bearing Mice: Implications for Cancer Detection 2

Cited by 90 publications

References 0 publications

Nuclear magnetic resonance measurement of skeletal muscle: anisotrophy of the diffusion coefficient of the intracellular water

Nuclear magnetic resonance measurement of skeletal muscle: anisotrophy of the diffusion coefficient of the intracellular water

Quantification of Nonenhancing Tumor Burden in Gliomas Using Effective T2 Maps Derived from Dual-Echo Turbo Spin-Echo MRI

Magnetic Resonance Imaging of Human Melanoma Xenograftsin Vivo: Proton Spin—lattice and Spin—spin Relaxation Times Versus Fractional Tumour Water Content and Fraction of Necrotic Tumour Tissue

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