A new NOE-mediated MT signal at around −1.6ppm for detecting ischemic stroke in rat brain

Abstract

In the present work, we reported a new nuclear Overhauser enhancement (NOE)-mediated magnetization transfer (MT) signal at around −1.6 ppm (NOE(−1.6)) in rat brain and investigated its application in the detection of acute ischemic stroke in rodent model. Using continuous wave (CW) MT sequence, the NOE(−1.6) is reliably detected in rat brain. The amplitude of this new NOE signal in rat brain was quantified using a 5-pool Lorentzian Z-spectral fitting method. Amplitudes of amide, amine, NOE at −3.5 ppm (NOE(−3.5)), as well as NOE(−1.6) were mapped using this fitting method in rat brain. Several other conventional imaging parameters (R 1 , R 2 , apparent diffusion coefficient (ADC), and semi-solid pool size ratio (PSR)) were also measured. Our results showed that NOE(−1.6), R 1 , R 2 , ADC, and APT signals from stroke lesion have significant changes at 0.5-1 h after stroke. Compared with several other imaging parameters, NOE(−1.6) shows the strongest contrast differences between stroke and contralateral normal tissues and stays consistent over time until 2 h after onset of stroke. Our results demonstrate that this new NOE(−1.6) signal in rat brain is a new potential contrast for assessment of acute stroke in vivo and might provide broad applications in the detection of other abnormal tissues.

Improving the detection sensitivity of pH‐weighted amide proton transfer MRI in acute stroke patients using extrapolated semisolid magnetization transfer reference signals

“…Therefore, the absolute MTR asym (3.5ppm) signal intensity as well as the contrast of the ischemic stroke is reduced by the upfield NOE signals and the use of the asymmetry metric reduces the sensitivity of APT signals in ischemic stroke imaging. It should be mentioned that, contrary to our findings and the basic evidence from studies on cells and tissue (53) and high resolution NMR studies of proteins (56, 57), others have not found a change of relayed-NOE signals following acute stroke (29, 58, 59). The most likely explanation of this is a difference in saturation power B 1 , leading to very different contributions of fast and slow exchanging protons to the Z-spectrum (60).…”

pH-sensitive MRI demarcates graded tissue acidification during acute stroke ― pH specificity enhancement with magnetization transfer and relaxation-normalized amide proton transfer (APT) MRI

“…Jones et al showed that in concentrated bovine serum albumin solution, both NOE and APT effects show pH dependence (Jones et al, 2013). On the other hand, Jin et al (Jin et al, 2013) and Zhang et al (Zhang et al, 2016) found very small NOE effect change following acute stroke. We would like to point out that Jones et al (Jones et al, 2013) used pulsed RF saturation scheme in volunteers and tumor patients, while Jin et al (Jin et al, 2013), Zhang et al (Zhang et al, 2016) and our study here used continuous wave saturation in acute ischemic animals.…”

“…On the other hand, Jin et al (Jin et al, 2013) and Zhang et al (Zhang et al, 2016) found very small NOE effect change following acute stroke. We would like to point out that Jones et al (Jones et al, 2013) used pulsed RF saturation scheme in volunteers and tumor patients, while Jin et al (Jin et al, 2013), Zhang et al (Zhang et al, 2016) and our study here used continuous wave saturation in acute ischemic animals. The differences in saturation schemes, diseases of interest, and the magnitude of pH change may partially explain the different conclusions of NOE contribution, which should be explored in the future.…”

“…Note that we chose a relatively long T 2MT similar to that used by Scheidegger et al, which allows the use of a simplified Lorentzian line shape to approximate the semi-solid MT contribution (Scheidegger et al, 2014). Because there is little overlap between NOE and APT effects, it is not necessary to include NOE in the simulation for the demonstration of relaxation-normalized APT MRI measurement (Jin et al, 2013; Zhang et al, 2016). …”

Diamagnetic chemical exchange saturation transfer (diaCEST) affords magnetic resonance imaging of extracellular matrix hydrogel implantation in a rat model of stroke

“…Ideally, an imaging method as an analytical tool will not require the addition of MR contrast agents and will directly detect the injected material and its degradation profile. Chemical exchange saturation transfer (CEST) is a versatile MR imaging approach [22, 23] that can selectively visualize the distribution of specific proteins and metabolites in vitro [24], in vivo in animal models [25], and also in human brain [26, 27]. CEST acquisition is performed with an off-resonance saturation pulse, similar to magnetization transfer (MT), where contrast can be observed in a wide frequency range (~100kHz).…”