Iopamidol as a responsive MRI‐chemical exchange saturation transfer contrast agent for pH mapping of kidneys: In vivo studies in mice at 7 T

Iopamidol (Isovue®—Bracco Diagnostic Inc.) is a clinically approved X‐Ray contrast agent used in the last 30 years for a wide variety of diagnostic applications with a very good clinical acceptance. Iopamidol contains two types of amide functionalities that can be exploited for the generation of chemical exchange saturation transfer effect. The exchange rate of the two amide proton pools is markedly pH‐dependent. Thus, a ratiometric method for pH assessment has been set‐up based on the comparison of the saturation transfer effects induced by selective irradiation of the two resonances. This ratiometric approach allows to rule out the concentration effect of the contrast agent and provides accurate pH measurements in the 5.5–7.4 range. Upon injection of Iopamidol into healthy mice, it has been possible to acquire pH maps of kidney regions. Furthermore, it has been also shown that the proposed method is able to report about pH‐changes induced in control mice fed with acidified or basified water for a period of a week before image acquisition. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Imaging pH using the chemical exchange saturation transfer (CEST) MRI: Correction of concomitant RF irradiation effects to quantify CEST MRI for chemical exchange rate and pH

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. © 2008 Wiley‐Liss, Inc.     

NOrmalized MAgnetization Ratio (NOMAR) filtering for creation of tissue selective contrast maps

An MRI segmentation technique based on collecting two additional saturation transfer images is proposed as an aid for improved detection of chemical exchange saturation transfer agents. In this approach, the additional images are acquired at saturation frequencies of ?12.5 and ?50 ppm. Use of the ratio of these images allows differentiation of voxels with low magnetization transfer contrast (such as fat, cerebrospinal fluid, edema, or blood) from target tissue voxels using a global threshold determined by histogram analysis. We demonstrate that this technique can reduce artifacts, in vitro, in a phantom containing tubes with chemical exchange saturation transfer contrast agent embedded in either crosslinked bovine serum albumin or buffer, and in vivo for detecting diamagnetic CEST (DIACEST) liposomes injected into mice. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Correction for artifacts induced by B(0) and B(1) field inhomogeneities in pH-sensitive chemical exchange saturation transfer (CEST) imaging.

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 B(0) and B(1) 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.     

Investigation of optimizing and translating pH‐sensitive pulsed‐chemical exchange saturation transfer (CEST) imaging to a 3T clinical scanner

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. © 2008 Wiley‐Liss, Inc.     

Fast multislice pH‐weighted chemical exchange saturation transfer (CEST) MRI with Unevenly segmented RF irradiation

Chemical exchange saturation transfer (CEST) MRI is a versatile imaging technique for measuring microenvironment properties via dilute CEST labile groups. Conventionally, CEST MRI is implemented with a long radiofrequency irradiation module, followed by fast image acquisition to obtain the steady state CEST contrast. Nevertheless, the sensitivity, scan time, and spatial coverage of the conventional CEST MRI method may not be optimal. Our study proposed a segmented radiofrequency labeling scheme that includes a long primary radiofrequency irradiation module to generate the steady state CEST contrast and repetitive short secondary radiofrequency irradiation module immediately after the image acquisition so as to maintain the steady state CEST contrast for multislice acquisition and signal averaging. The proposed CEST MRI method was validated experimentally with a tissue‐like pH phantom and optimized for the maximal contrast‐to‐noise ratio. In addition, the proposed sequence was evaluated for imaging ischemic acidosis via pH‐weighted endogenous amide proton transfer MRI, which showed similar contrast as conventional amide proton transfer MRI. In sum, a fast multislice relaxation self‐compensated CEST MRI sequence was developed, with significantly improved sensitivity and suitable for in vivo applications. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.