Presentation of microstructural diffusion components by color schemes in abdominal organs.

PURPOSE: Development of a color scheme representation to facilitate the interpretation of tri-exponential DWI data from abdominal organs, where multi-exponential behavior is more pronounced. METHODS: Multi-exponential analysis of DWI data provides information about the microstructure of the tissue under study. The tri-exponential signal analysis generates numerous parameter images that are difficult to analyze individually. Summarized color images can simplify at-a-glance analysis. A color scheme was developed in which the slow, intermediate, and fast diffusion components were each assigned to a different red, green, and blue color channel. To improve the appearance of the image, histogram equalization, gamma correction, and white balance were used, and the processing parameters were adjusted. Examples of the resulting color maps of the diffusion fractions of healthy and pathological kidney and prostate are shown. RESULTS: The color maps obtained by the presented method show the merged information of the slow, intermediate, and fast diffusion components in a single view. A differentiation of the different fractions becomes clearly visible. Fast diffusion regimes, such as in the renal hilus, can be clearly distinguished from slow fractions, such as in dense tumor tissue. CONCLUSION: Combining the diffusion information from tri-exponential DWI analysis into a single color image allows for simplified interpretation of the diffusion fractions. In the future, such color images may provide additional information about the microstructural nature of the tissue under study.

Image downsampling expedited adaptive least-squares (IDEAL) fitting improves intravoxel incoherent motion (IVIM) analysis in the human kidney.

PURPOSE: To improve the reliability of intravoxel incoherent motion (IVIM) model parameter estimation for the DWI in the kidney using a novel image downsampling expedited adaptive least-squares (IDEAL) approach. METHODS: The robustness of IDEAL was investigated using simulated DW-MRI data corrupted with different levels of Rician noise. Subsequently, the performance of the proposed method was tested by fitting bi- and triexponential IVIM model to in vivo renal DWI data acquired on a clinical 3 Tesla MRI scanner and compared to conventional approaches (fixed D* and segmented fitting). RESULTS: The numerical simulations demonstrated that the IDEAL algorithm provides robust estimates of the IVIM parameters in the presence of noise (SNR of 20) as indicated by relatively low absolute percentage bias (maximal sMdPB <20%) and normalized RMSE (maximal RMSE <28%). The analysis of the in vivo data showed that the IDEAL-based IVIM parameter maps were less noisy and more visually appealing than those obtained using the fixed D* and segmented methods. Further, coefficients of variation for nearly all IVIM parameters were significantly reduced in cortex and medulla for IDEAL-based biexponential (coefficients of variation: 4%-50%) and triexponential (coefficients of variation: 7.5%-75%) IVIM modelling compared to the segmented (coefficients of variation: 4%-120%) and fixed D* (coefficients of variation: 17%-174%) methods, reflecting greater accuracy of this method. CONCLUSION: The proposed fitting algorithm yields more robust IVIM parameter estimates and is less susceptible to poor SNR than the conventional fitting approaches. Thus, the IDEAL approach has the potential to improve the reliability of renal DW-MRI analysis for clinical applications.

Noninvasive assessment of renal dynamics and pH in a unilateral ureter obstruction model using DCE MR-CEST urography.

PURPOSE: To assess the potential of DCE MR CEST urography for assessing renal function in mice with unilateral ureter obstruction (UUO) by simultaneous pH and renal uptake/clearance measurements following injection of iopamidol. METHODS: The right ureter of nine mice was obstructed via suture ligation. The animals were imaged at day 1, 2, and 3 post-obstruction on an 11.7T MRI scanner. Ninety-six sets of saturated CEST images at 4.3 and 5.5 ppm were collected. Renal pH values were obtained by calculating the signal ratio for these two frequencies and using a pH calibration curve. Renal time activity curves were measured as a percentage change in the post-injection CEST signal at 4.3 ppm relative to the average pre-injection signal. RESULTS: For the healthy mice, the time activity curves of both kidneys were nearly identical and displayed rapid excretion of contrast. For the UUO mice, the dynamic CEST curves for the obstructed kidneys displayed prolonged time to peak (TTP) values and delayed contrast excretion compared with the contralateral (CL) kidneys. Renal pH maps of the healthy animals showed similar acidic values for both kidneys (pH 6.65 ± 0.04 vs 6.67 ± 0.02), whereas in the obstructed kidneys there was a significant increase in pH values compared with the CL kidneys (pH 6.67 ± 0.08 vs 6.79 ± 0.11 in CL and UUO kidneys, respectively). CONCLUSION: Our findings indicate that DCE-MR-CEST urography can detect changes in renal uptake/excretion and pH homeostasis and distinguish between obstructed and unobstructed kidney as early as 1 day after UUO.

A snapshot of the vast array of diamagnetic CEST MRI contrast agents.

Since the inception of CEST MRI in the 1990s, a number of compounds have been identified as suitable for generating contrast, including paramagnetic lanthanide complexes, hyperpolarized atom cages and, most interesting, diamagnetic compounds. In the past two decades, there has been a major emphasis in this field on the identification and application of diamagnetic compounds that have suitable biosafety profiles for usage in medical applications. Even in the past five years there has been a tremendous growth in their numbers, with more and more emphasis being placed on finding those that can be ultimately used for patient studies on clinical 3 T scanners. At this point, a number of endogenous compounds present in tissue have been identified, and also natural and synthetic organic compounds that can be administered to highlight pathology via CEST imaging. Here we will provide a very extensive snapshot of the types of diamagnetic compound that can generate CEST MRI contrast, together with guidance on their utility on typical preclinical and clinical scanners and a review of the applications that might benefit the most from this new technology.

Exploring the potential of the novel imidazole-4,5-dicarboxyamide chemical exchange saturation transfer scaffold for pH and perfusion imaging.

Here, we describe and assess the potential of 14 newly synthesized imidazole-4,5-dicarboxyamides (I45DCs) for pH and perfusion imaging. A number of these aromatic compounds possess large labile proton chemical shifts (up to 7.7 ppm from water) because of their intramolecular hydrogen bonds and a second labile proton to allow for chemical exchange saturation transfer (CEST) signal ratio-based pH measurements. We have found that the contrast produced is strong for a wide range of substitutions and that the inflection points in the CEST signal ratio versus pH plots used to generate concentration-independent pH maps can be adjusted based on these subsitutions to tune the pH range that can be measured. These I45DC CEST agents have advantages over the triiodobenzenes currently employed for tumor and kidney pH mapping, both preclinically and in initial human studies. Finally, as CEST MRI combined with exogenous contrast has the potential to detect functional changes in the kidneys, we evaluated our highest performing anionic compound (I45DC-diGlu) on a unilateral urinary obstruction mouse model and observed lower contrast uptake in the obstructed kidney compared with the unobstructed kidney and that the unobstructed kidney displayed a pH of ~ 6.5 while the obstructed kidney had elevated pH and an increased range in pH values. Based on this, we conclude that the I45DCs have excellent imaging properties and hold promise for a variety of medical imaging applications, particularly renal imaging.

Probing Renal Microstructure and Function with Advanced Diffusion MRI: Concepts, Applications, Challenges, and Future Directions.

Diffusion measurements in the kidney are affected not only by renal microstructure but also by physiological processes (i.e., glomerular filtration, water reabsorption, and urine formation). Because of the superposition of passive tissue diffusion, blood perfusion, and tubular pre-urine flow, the limitations of the monoexponential apparent diffusion coefficient (ADC) model in assessing pathophysiological changes in renal tissue are becoming apparent and motivate the development of more advanced diffusion-weighted imaging (DWI) variants. These approaches take advantage of the fact that the length scale probed in DWI measurements can be adjusted by experimental parameters, including diffusion-weighting, diffusion gradient directions and diffusion time. This forms the basis by which advanced DWI models can be used to capture not only passive diffusion effects, but also microcirculation, compartmentalization, tissue anisotropy. In this review, we provide a comprehensive overview of the recent advancements in the field of renal DWI. Following a short introduction on renal structure and physiology, we present the key methodological approaches for the acquisition and analysis of renal DWI data, including intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI), non-Gaussian diffusion, and hybrid IVIM-DTI. We then briefly summarize the applications of these methods in chronic kidney disease and renal allograft dysfunction. Finally, we discuss the challenges and potential avenues for further development of renal DWI. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

Renal MRI: From Nephron to NMR Signal.

Renal diseases pose a significant socio-economic burden on healthcare systems. The development of better diagnostics and prognostics is well-recognized as a key strategy to resolve these challenges. Central to these developments are MRI biomarkers, due to their potential for monitoring of early pathophysiological changes, renal disease progression or treatment effects. The surge in renal MRI involves major cross-domain initiatives, large clinical studies, and educational programs. In parallel with these translational efforts, the need for greater (patho)physiological specificity remains, to enable engagement with clinical nephrologists and increase the associated health impact. The ISMRM 2022 Member Initiated Symposium (MIS) on renal MRI spotlighted this issue with the goal of inspiring more solutions from the ISMRM community. This work is a summary of the MIS presentations devoted to: 1) educating imaging scientists and clinicians on renal (patho)physiology and demands from clinical nephrologists, 2) elucidating the connection of MRI parameters with renal physiology, 3) presenting the current state of leading MR surrogates in assessing renal structure and functions as well as their next generation of innovation, and 4) describing the potential of these imaging markers for providing clinically meaningful renal characterization to guide or supplement clinical decision making. We hope to continue momentum of recent years and introduce new entrants to the development process, connecting (patho)physiology with (bio)physics, and conceiving new clinical applications. We envision this process to benefit from cross-disciplinary collaboration and analogous efforts in other body organs, but also to maximally leverage the unique opportunities of renal physiology. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

calf - Software for CEST Analysis with Lorentzian Fitting.

Analysis of chemical exchange saturation transfer (CEST) MRI data requires sophisticated methods to obtain reliable results about metabolites in the tissue under study. CEST generates z-spectra with multiple components, each originating from individual molecular groups. The individual lines with Lorentzian line shape are mostly overlapping and disturbed by various effects. We present an elaborate method based on an adaptive nonlinear least squares algorithm that provides robust quantification of z-spectra and incorporates prior knowledge in the fitting process. To disseminate CEST to the research community, we developed software as part of this study that runs on the Microsoft Windows operating system and will be made freely available to the community. Special attention has been paid to establish a low entrance threshold and high usability, so that even less experienced users can successfully analyze CEST data.

Lorentzian-Corrected Apparent Exchange-Dependent Relaxation (LAREX) Ω-Plot Analysis-An Adaptation for qCEST in a Multi-Pool System: Comprehensive In Silico, In Situ, and In Vivo Studies.

Based on in silico, in situ, and in vivo studies, this study aims to develop a new method for the quantitative chemical exchange saturation transfer (qCEST) technique considering multi-pool systems. To this end, we extended the state-of-the-art apparent exchange-dependent relaxation (AREX) method with a Lorentzian correction (LAREX). We then validated this new method with in situ and in vivo experiments on human intervertebral discs (IVDs) using the Kendall-Tau correlation coefficient. In the in silico experiments, we observed significant deviations of the AREX method as a function of the underlying exchange rate (kba) and fractional concentration (fb) compared to the ground truth due to the influence of other exchange pools. In comparison to AREX, the LAREX-based Ω-plot approach yielded a substantial improvement. In the subsequent in situ and in vivo experiments on human IVDs, no correlation to the histological reference standard or Pfirrmann classification could be found for the fb (in situ: τ = −0.17 p = 0.51; in vivo: τ = 0.13 p = 0.30) and kba (in situ: τ = 0.042 p = 0.87; in vivo: τ = −0.26 p = 0.04) of Glycosaminoglycan (GAG) with AREX. In contrast, the influence of interfering pools could be corrected by LAREX, and a moderate to strong correlation was observed for the fractional concentration of GAG for both in situ (τ = −0.71 p = 0.005) and in vivo (τ = −0.49 p < 0.001) experiments. The study presented here is the first to introduce a new qCEST method that enables qCEST imaging in systems with multiple proton pools.

Spectral diffusion analysis of kidney intravoxel incoherent motion MRI in healthy volunteers and patients with renal pathologies.

PURPOSE: To assess the feasibility of measuring tubular and vascular signal fractions in the human kidney using nonnegative least-square (NNLS) analysis of intravoxel incoherent motion data collected in healthy volunteers and patients with renal pathologies. METHODS: MR imaging was performed at 3 Tesla in 12 healthy subjects and 3 patients with various kidney pathologies (fibrotic kidney disease, failed renal graft, and renal masses). Relative signal fractions f and mean diffusivities of the diffusion components in the cortex, medulla, and renal lesions were obtained using the regularized NNLS fitting of the intravoxel incoherent motion data. Test-retest repeatability of the NNLS approach was tested in 5 volunteers scanned twice. RESULTS: In the healthy kidneys, the NNLS method yielded diffusion spectra with 3 distinguishable components that may be linked to the slow tissue water diffusion, intermediate tubular and vascular flow, and fast blood flow in larger vessels with the relative signal fractions, fslow , finterm and ffast , respectively. In the pathological kidneys, the diffusion spectra varied substantially from those acquired in the healthy kidneys. Overall, the renal cyst showed substantially higher finterm and lower fslow , whereas the fibrotic kidney, failed renal graft, and renal cell carcinoma demonstrated the opposite trend. CONCLUSION: NNLS-based intravoxel incoherent motion could potentially become a valuable tool in assessing changes in tubular and vascular volume fractions under pathophysiological conditions.

Feasibility of quantitative susceptibility mapping (QSM) of the human kidney.

OBJECTIVE: To evaluate the feasibility of in-vivo quantitative susceptibility mapping (QSM) of the human kidney. METHODS: An axial single-breath-hold 3D multi-echo sequence (acquisition time 33 s) was completed on a 3 T-MRI-scanner (Magnetom Prisma, Siemens Healthineers, Erlangen, Germany) in 19 healthy volunteers. Graph-cut-based unwrapping combined with the T2*-IDEAL approach was performed to remove the chemical shift of fat and to quantify QSM of the upper abdomen. Mean susceptibility values of the entire, renal cortex and medulla in both kidneys and the liver were determined and compared. Five subjects were measured twice to examine the reproducibility. One patient with severe renal fibrosis was included in the study to evaluate the potential clinical relevance of QSM. RESULTS: QSM was successful in 17 volunteers and the patient with renal fibrosis. Anatomical structures in the abdomen were clearly distinguishable by QSM and the susceptibility values obtained in the liver were comparable to those found in the literature. The results showed a good reproducibility. Besides, the mean renal QSM values obtained in healthy volunteers (0.04 ± 0.07 ppm for the right and - 0.06 ± 0.19 ppm for the left kidney) were substantially higher than that measured in the investigated fibrotic kidney (- 0.43 ± - 0.02 ppm). CONCLUSION: QSM of the human kidney could be a promising approach for the assessment of information about microscopic renal tissue structure. Therefore, it might further improve functional renal MR imaging.

Detection of early cartilage degeneration in the tibiotalar joint using 3 T gagCEST imaging: a feasibility study.

OBJECTIVE: To establish and optimize a stable 3 Tesla (T) glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging protocol for assessing the articular cartilage of the tibiotalar joint in healthy volunteers and patients after a sustained injury to the ankle. METHODS: Using Bloch-McConnell simulations, we optimized the sequence protocol for a 3 T MRI scanner for maximum gagCEST effect size within a clinically feasible time frame of less than 07:30 min. This protocol was then used to analyze the gagCEST effect of the articular cartilage of the tibiotalar joint of 17 healthy volunteers and five patients with osteochondral lesions of the talus following ankle trauma. Reproducibility was tested with the intraclass correlation coefficient. RESULTS: The mean magnetization transfer ratio asymmetry (MTRasym), i.e., the gagCEST effect size, was significantly lower in patients than in healthy volunteers (0.34 ± 1.9% vs. 1.49 ± 0.11%; p < 0.001 [linear mixed model]). Intra- and inter-rater reproducibility was excellent with an average measure intraclass correlation coefficient (ICC) of 0.97 and a single measure ICC of 0.91 (p < 0.01). DISCUSSION: In this feasibility study, pre-morphological tibiotalar joint cartilage damage was quantitatively assessable on the basis of the optimized 3 T gagCEST imaging protocol that allowed stable quantification gagCEST effect sizes across a wide range of health and disease in clinically feasible acquisition times.

Analysis of different image-registration algorithms for Fourier decomposition MRI in functional lung imaging.

BACKGROUND: Motion correction is mandatory for the functional Fourier decomposition magnetic resonance imaging (FD-MRI) of the lungs. Therefore, it is important to evaluate the quality of various image-registration algorithms for pulmonary FD-MRI and to determine their impact on FD-MRI outcome. PURPOSE: To evaluate different image-registration algorithms for FD-MRI in functional lung imaging. MATERIAL AND METHODS: Fifteen healthy volunteers were examined in a 1.5-T whole-body MR scanner (Magnetom Avanto, Siemens AG) with a non-contrast enhanced 2D TrueFISP pulse sequence in coronal view and free-breathing (acquisition time 45 s, 250 images). Three image-registration algorithms were used to compensate the spatial variation of the lungs (fMRLung 3.0, ANTs, and Elastix). Quality control for image registration was performed by edge detection (ED), quotient image criterion (QI), and dice similarity coefficient (DSC). Ventilation, perfusion, and a ventilation/perfusion quotient (V/Q) were calculated using the three registered datasets. RESULTS: Average computing times for the three image-registration algorithms were 1.0 ± 1.6 min, 38.0 ± 13.5 min, and 354 ± 78 min for fMRLung, ANTs, and Elastix, respectively. No significant difference in the quality of motion correction provided by different image-registration algorithms occurred. Significant differences were observed between fMRLung- and Elastix-based perfusion values ​​of the left lung as well as fMRLung- and ANTs-based V/Q quotient of the right and the entire lung (P < 0.05). Other ventilation and perfusion values were not significantly different. CONCLUSION: The mandatory motion correction for functional FD-MRI of the lung can be achieved through different image-registration algorithms with consistent quality. However, a significantly difference in computing time between the image-registration algorithms still requires an optimization.

Comparison of PGSE and STEAM DTI acquisitions with varying diffusion times for probing anisotropic structures in human kidneys.

PURPOSE: To evaluate the sensitivity of stimulated-echo acquisition mode (STEAM) and pulsed-gradient spin-echo (PGSE) diffusion tensor imaging (DTI) acquisitions with different diffusion times for measuring renal tissue anisotropy. METHODS: Twelve healthy volunteers underwent an MRI examination at a 3T scanner including STEAM and PGSE DTI with variable diffusion times Δ (20.3, 37 and 125 ms). Three volunteers were scanned twice to test the reproducibility for repeated examinations. Diffusion parameters fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in the automatically segmented cortical and medullary regions of interests in both kidneys were calculated and averaged over all subjects for further analysis. Moreover, 5-grade qualitative evaluation of the FA and ADC maps from each sequence was conducted by two experienced radiologists in a consensus. RESULTS: The cortex-medulla difference in the STEAM sequence was significantly higher than that in PGSE with short ∆ = 20.3 ms (P < 0.001) and in PGSE with intermediate ∆ = 37 ms (P < 0.05) diffusion times. Reproducibility of the FA/ADC measurements was very good and comparable for all acquisition modes investigated. For the FA maps, the PGSE sequence with intermediate diffusion time scored highest in the subjective visual assessment of radiologists. CONCLUSION: The delineation of anisotropy in renal tissue is depending on the used diffusion time of the DTI sequence. A PGSE acquisition at a diffusion time of about 37 ms provides reproducible results with optimal corticomedullary contrast in FA and ADC maps and good image quality.

Analysis of different phase unwrapping methods to optimize quantitative susceptibility mapping in the abdomen.

PURPOSE: Quantitative susceptibility mapping (QSM) is heavily impacted by phase processing of gradient echo imaging data. So far, phase unwrapping algorithms have mostly been developed and tested for neuroimaging applications. In this work, a numerical human abdomen phantom was created and used to assess the feasibility of different phase unwrapping algorithms in abdominal QSM. Furthermore, in vivo data were acquired to evaluate consistency with the simulations. METHODS: Laplacian-based, quality-guided region growing and graph-cuts unwrapping techniques were evaluated using the numerical phantom as well as an in vivo measurement. As a quality metric, root mean square error (RMSE) was calculated in order to analyze the performance of the examined unwrapping algorithms. Subsequently, susceptibility maps were generated from the resulting phase maps and compared to the ground truth. The evaluation was carried out on the whole phantom as well as individual organs. RESULTS: Graph-cuts led to the most accurate and robust results among the investigated unwrapping methods. The other algorithms showed severe errors in regions with large susceptibility changes (i.e., around the lungs). Deviations from the ground-truth susceptibility were higher than in the previous brain simulations for all tested algorithms. CONCLUSION: Graph-cuts-based unwrapping algorithms should be preferred in QSM studies in the human abdomen, where large susceptibility changes occur. For further improvement of QSM studies, unwrapping algorithms should be optimized for abdominal applications.

Proton exchange in aqueous urea solutions measured by water-exchange (WEX) NMR spectroscopy and chemical exchange saturation transfer (CEST) imaging in vitro.

PURPOSE: To characterize the proton exchange in aqueous urea solutions using a modified version of the WEX II filter at high magnetic field, and to assess the feasibility of performing quantitative urea CEST MRI on a 3T clinical MR system. METHODS: In order to study the dependence of the exchange-rate constant ksw of urea as a function of pH and T, the WEX-spectra were acquired at 600 MHz from urea solutions in a pH range from 6.4 to 8.0 and a temperature range from T=22∘C to 37∘C . The CEST experiments were performed on a 3T MRI scanner by applying a train of 50 Gaussian-shaped pulses, each 100-millisecond long with a spacing of 100 milliseconds, for saturation. Exchange rates of urea were calculated using the (extended) AREX metric. RESULTS: The results showed that proton exchange in aqueous urea solutions is acid and base catalyzed with the rate constants: ka=(9.95±1.1)×106 l/(mol·s) and kb=(6.21±0.21)×106 l/(mol·s), respectively. Since the urea protons undergo a slow exchange with water protons, the CEST effect of urea can be observed efficiently at 3T. However, in neutral solutions the exchange rate of urea is minimal and cannot be estimated using the quantitative CEST approach. CONCLUSIONS: By means of the WEX-spectroscopy, the kinetic parameters of the proton exchange in urea solutions have been determined. It was also possible to estimate the exchange rates of urea in a broad range of pH values using the CEST method at a clinical scanner.

Comparison of B0 versus B0 and B1 field inhomogeneity correction for glycosaminoglycan chemical exchange saturation transfer imaging.

PURPOSE: The study compares glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging of intervertebral discs corrected for solely B0 inhomogeneities or both B0 and B1 inhomogeneities. METHODS: Lumbar intervertebral discs of 20 volunteers were examined with T2-weighted and gagCEST imaging. Field inhomogeneity correction was performed with B0 correction only and with correction of both B0 and B1. GagCEST effects measured by the asymmetric magnetization transfer ratio (MTRasym) and signal-to-noise ratio (SNR) were compared between both methods. RESULTS: Significant higher MTRasym and SNR values were obtained in the nucleus pulposus using B0 and B1 correction compared with B0-corrected gagCEST. The GagCEST effect was significantly different in the nucleus pulposus compared with the annulus fibrosus for both methods. CONCLUSION: The B0 and B1 field inhomogeneity correction method leads to an improved quality of gagCEST imaging in IVDs compared with only B0 correction.

Quantitative pulsed CEST-MRI at a clinical 3T MRI system.

OBJECTIVES: The goal of this study was to quantify CEST related parameters such as chemical exchange rate and fractional concentration of exchanging protons at a clinical 3T scanner. For this purpose, two CEST quantification approaches-the AREX metric (for 'apparent exchange dependent relaxation'), and the AREX-based Ω-plot method were used. In addition, two different pulsed RF irradiation schemes, using Gaussian-shaped and spin-lock pulses, were compared. MATERIALS AND METHODS: Numerical simulations as well as MRI measurements in phantoms were performed. For simulations, the Bloch-McConnell equations were solved using a two-pool exchange model. MR experiments were performed on a clinical 3T MRI scanner using a cylindrical phantom filled with creatine solution at different pH values and different concentrations. RESULTS: The validity of the Ω-plot method and the AREX approach using spin-lock preparation for determination of the quantitative CEST parameters was demonstrated. Especially promising results were achieved for the Ω-plot method when the spin-lock preparation was employed. CONCLUSION: Pulsed CEST at 3T could be used to quantify parameters such as exchange rate constants and concentrations of protons exchanging with free water. In the future this technique might be used to estimate the exchange rates and concentrations of biochemical substances in human tissues in vivo.

The Proton Resonance Enhancement for CEST imaging and Shift Exchange (PRECISE) family of RF pulse shapes for Chemical Exchange Saturation Transfer MRI.

Purpose: To optimize a 100 msec pulse for producing CEST MRI contrast and evaluate in mice. Methods: A gradient ascent algorithm was employed to generate a family of 100 point, 100 msec pulses for use in CEST pulse trains ('PRECISE'). Gradient ascent optimizations were performed for exchange rates (k ca ) = 500 s -1 , 1,500 s -1 , 2,500 s -1 , 3,500 s -1 and 4,500 s -1 and offsets (Δω) = 9.6, 7.8, 4.2 and 2.0 ppm. 7 PRECISE pulse shapes were tested on an 11.7 T scanner using a phantom containing three representative CEST agents with peak saturation B 1 = 4 µT. The pulse producing the most contrast in phantoms was then evaluated for CEST MRI pH mapping of the kidneys in healthy mice after iopamidol administration. Results: The most promising pulse in terms of contrast performance across all three phantoms was the 9.6 ppm, 2500 s -1 optimized pulse with ∼2.7 x improvement over Gaussian and ∼1.3x's over Fermi pulses. This pulse also displayed a large improvement in contrast over the Gaussian pulse after administration of iopamidol in live mice. Conclusion: A new 100 msec pulse was developed based on gradient ascent optimizations which produced better contrast compared to standard Gaussian and Fermi pulses in phantoms. This shape also showed a substantial improvement for CEST MRI pH mapping in live mice over the Gaussian shape and appears promising for a wide range of CEST applications.