Evidence for the Role of Intracellular Water Lifetime as a Tumour Biomarker Obtained by In Vivo Field‐Cycling Relaxometry

Abstract

It was established through in vivo T 1 measurements at lowm agnetic fields that tumour cells displayp roton T 1 values that are markedly longer than those shown by healthy tissue.M oreover,i th as been found that the elongation of T 1 parallels the aggressiveness of the investigated tumour.The T 1 lengthening is associated with an enhanced water exchange rate across the transcytolemmal membrane through an overexpression/upregulation of GLUT1 and Na + /K + ATPase transporters.I tf ollows that the intracellular water lifetime represents ah allmark of tumour cells that can be easily monitored by measuring T 1 at different magnetic field strengths ranging from 0.2 to 200 mT.Magnetic resonance imaging (MRI) has played ak ey role in the field of oncology over the last few decades.T he prominent role of MRI relies on its superb spatial and temporal resolution, and its diagnostic power basically arises from the differences in the longitudinal (T 1 )a nd transverse (T 2 )p roton relaxation times between healthy and pathological tissues.H owever, at the magnetic field strength of the currently available MRI scanners,changes in T 1 do not appear to be sensitive enough to report on the particular aspects of the tumour stage. [1] However,t here is widespread opinion that at low magnetic field strength, the marked increase in R 1 (= 1/T 1 )o bserved in biological tissues might be beneficial towards improving the MRI diagnostic potential in tumour phenotyping. [2] Herein, it is shown that the in vivo acquisition of 1/T 1 nuclear magnetic resonance dispersion (NMRD) profiles (from 0.2 to 200 mT) fully supports this expectation as the observed R 1 values at low magnetic fields (< 0.2 T) enable the clear discrimination between tumours characterised by different metastatic potentials.The1 / T 1 NMRD profiles were acquired on fast field cycling (FFC) relaxometers,w hich are able to switch the Figure 1. A) The FFC experiment:T he nuclear spin polarization is built up during the pre-polarization phase, at B p .R elaxation occurs during the evolution period (t)atB r ,t hen the NMR signal is detected at B d . The sequence is repeated,s taggering t each time. ForB r > 7MHz, the cycle starts in the absence of any polarization field. B) Photographs of the FFC-NMR relaxometer showing the introducedm odificationsfor the in vivo acquisition:a)the FFC magnet;b)the mouse holding system;c )the transmitter/receiver coil around the mouse'sl eg.

Estimation of cellular‐interstitial water exchange in dynamic contrast enhanced MRI using two flip angles

“…In the case of cancer cells, a wide range of τ i values between 15 ms and 2.3 s has been reported from DCE-MRI measurements. 13,14,19,20,49,50 Heterogeneous and rapidly changing nature of cancer cells can be one of the reasons why such a wide range of τ i values can be observed. In addition, this can also be due to the inherent uncertainty of τ i measurement using conventional DCE-MRI and contrast kinetic models, which has been one of the main obstacles hindering the use of the potentially important parameter τ i for clinical and research applications.…”

Comparison of fast field-cycling magnetic resonance imaging methods and future perspectives

“…These examples illustrate the excellent image quality that FFC-MRI can provide, and initial biomedical evaluation of the translation from FFC-NMR to FFC-MRI. In the future, it is expected that the successful biological applications of FFC-NMR [64] will be translated to FFC-MRI, leading to new imaging biomarkers of diseases that still remain to be validated and compared to the already rich contrast available on conventional fixed-field MRI systems. Figure 11.…”

Joint multi‐field T1 quantification for fast field‐cycling MRI

“…1,2 In recent years, the T 1 dispersion of protons in particular has experienced increased interest for the investigation of biomarkers related to various pathological processes. [3][4][5][6] The field-dependent properties of such biomarkers are invisible to traditional MRI scanners, which operate only at one fixed main magnetic field strength and are restricted to the measurement of relaxation times corresponding to the B 0 field used. However, new MRI-derived technologies are emerging that allow exploring different magnetic fields within a single system.…”

“…The magnetic field dependency of the longitudinal and transverse relaxation times, also referred to as nuclear magnetic relaxation dispersion (NMRD), provides insight into the underlying structural order and dynamics of a wide range of molecular systems 1,2 . In recent years, the dispersion of protons in particular has experienced increased interest for the investigation of biomarkers related to various pathological processes 3‐6 . The field‐dependent properties of such biomarkers are invisible to traditional MRI scanners, which operate only at one fixed main magnetic field strength and are restricted to the measurement of relaxation times corresponding to the field used.…”