Amide proton transfer‐weighted (APTw) MR imaging shows promise as a biomarker of brain tumor status. Currently used APTw MRI pulse sequences and protocols vary substantially among different institutes, and there are no agreed‐on standards in the imaging community. Therefore, the results acquired from different research centers are difficult to compare, which hampers uniform clinical application and interpretation. This paper reviews current clinical APTw imaging approaches and provides a rationale for optimized APTw brain tumor imaging at 3 T, including specific recommendations for pulse sequences, acquisition protocols, and data processing methods. We expect that these consensus recommendations will become the first broadly accepted guidelines for APTw imaging of brain tumors on 3 T MRI systems from different vendors. This will allow more medical centers to use the same or comparable APTw MRI techniques for the detection, characterization, and monitoring of brain tumors, enabling multi‐center trials in larger patient cohorts and, ultimately, routine clinical use.

Chemical exchange saturation transfer (CEST) imaging provides an indirect detection mechanism that allows quantification of certain labile groups unobservable using conventional MRI. Recently, amide proton transfer (APT) imaging, a variant form of CEST imaging, has been shown capable of detecting lactic acidosis during acute ischemia, providing information complementary to that of perfusion and diffusion MRI. However, CEST contrast is usually small, and therefore, it is important to optimize experimental conditions for reliable and quantitative CEST imaging. In particular, CEST imaging is sensitive to B₀ and B₁ field, while on the other hand; field inhomogeneities persist despite recent advances in magnet technologies, especially for in vivo imaging at high fields. Consequently, correction algorithms that can compensate for field inhomogeneity‐induced measurement errors in CEST imaging might be very useful. In this study, the dependence of CEST contrast on field distribution was solved and a correction algorithm was developed to compensate for field inhomogeneity‐induced CEST imaging artifacts. In addition, the proposed algorithm was verified with both numerical simulation and experimental measurements, and showed nearly complete correction of CEST imaging measurement errors caused by moderate field inhomogeneity. Magn Reson Med, 2007.

The ischemic tissue becomes acidic after initiation of anaerobic respiration, which may result in impaired tissue metabolism and, ultimately, in severe tissue damage. Although changes in the major cerebral metabolites can be studied using magnetic resonance (MR) spectroscopy (MRS)-based techniques, their spatiotemporal resolution is often not sufficient for routine examination of fast-evolving and heterogeneous acute stroke lesions. Recently, pH-weighted MR imaging (MRI) has been proposed as a means to assess tissue acidosis by probing the pH-dependent chemical exchange of amide protons from endogenous proteins and peptides. In this study, we characterized acute ischemic tissue damage using localized proton MRS and multiparametric imaging techniques that included perfusion, diffusion, pH, and relaxation MRI. Our study showed that pH-weighted MRI can detect ischemic lesions and strongly correlates with tissue lactate content measured by ¹H MRS, indicating lactic acidosis. Our results also confirmed the correlation between apparent diffusion coefficient and lactate; however, no significant relationship was found for perfusion, T₁, and T₂. In summary, our study showed that optimized endogenous pH-weighted MRI, by sensitizing to local tissue pH, remains a promising tool for providing a surrogate imaging marker of lactic acidosis and altered tissue metabolism, and augments conventional techniques for stroke diagnosis.

Chemical exchange saturation transfer (CEST) MRI provides a sensitive detection mechanism that allows characterization of dilute labile protons usually undetectable by conventional MRI. Particularly, amide proton transfer (APT) imaging, a variant of CEST MRI, has been shown capable of detecting ischemic acidosis, and may serve as a surrogate metabolic imaging marker. For preclinical CEST imaging, continuous‐wave (CW) radiofrequency (RF) irradiation is often applied so that the steady state CEST contrast can be reached. On clinical scanners, however, specific absorption rate (SAR) limit and hardware preclude the use of CW irradiation, and instead require an irradiation scheme of repetitive RF pulses (pulsed‐CEST imaging). In this work, CW‐ and pulsed‐CEST MRI were systematically compared using a tissue‐like pH phantom on an imager capable of both CW and pulsed RF irradiation schemes. The results showed that the maximally obtainable pulsed‐CEST contrast is approximately 95% of CW‐CEST contrast, and their optimal RF irradiation powers are equal. Moreover, the pulsed‐CEST sequence was translated to a 3 Tesla clinical scanner and detected pH contrast from the labile creatine amine groups (1.9 ppm). Furthermore, pilot endogenous APT imaging of normal human volunteers was demonstrated, warranting future APT MRI of stroke patients to elucidate its diagnostic value. Magn Reson Med 60:834–841, 2008.

Chemical exchange saturation transfer (CEST) MRI is a versatile imaging method that probes the chemical exchange between bulk water and exchangeable protons. CEST imaging indirectly detects dilute labile protons via bulk water signal changes following selective saturation of exchangeable protons, which offers substantial sensitivity enhancement and has sparked numerous biomedical applications. Over the past decade, CEST imaging techniques have rapidly evolved owing to contributions from multiple domains, including the development of CEST mathematical models, innovative contrast agent designs, sensitive data acquisition schemes, efficient field inhomogeneity correction algorithms, and quantitative CEST (qCEST) analysis. The CEST system that underlies the apparent CEST‐weighted effect, however, is complex. The experimentally measurable CEST effect depends not only on parameters such as CEST agent concentration, pH and temperature, but also on relaxation rate, magnetic field strength and more importantly, experimental parameters including repetition time, RF irradiation amplitude and scheme, and image readout. Thorough understanding of the underlying CEST system using qCEST analysis may augment the diagnostic capability of conventional imaging. In this review, we provide a concise explanation of CEST acquisition methods and processing algorithms, including their advantages and limitations, for optimization and quantification of CEST MRI experiments. Copyright © 2015 John Wiley & Sons, Ltd.

Chemical exchange saturation transfer (CEST) MRI has been shown capable of detecting dilute labile protons and abnormal tissue glucose/oxygen metabolism, and thus, may serve as a complementary imaging technique to the conventional MRI methods. CEST imaging, however, is also dependent on experimental parameters such as the power, duration, and waveform of the irradiation RF pulse. As a result, its sensitivity and specificity for microenvironment properties such as pH is not optimal. In this study, the dependence of CEST contrast on experimental parameters was solved and an iterative compensation algorithm was proposed that corrects the experimentally measured CEST contrast from the concomitant RF irradiation effects. The proposed algorithm was verified with both numerical simulation and experimental measurements from a tissue‐like pH phantom, and showed that pH derived from the compensated CEST imaging agrees reasonably well with pH‐electrode measurements within 0.1 pH unit. In sum, our study validates the use of a correction algorithm to compensate CEST imaging from concomitant RF irradiation effects for accurate calibration of the chemical exchange rate, and demonstrates the feasibility of pH imaging with CEST MRI. Magn Reson Med 60:390–397, 2008.