Lactate Metabolism in Human Lung Tumors.

Cancer cells consume glucose and secrete lactate in culture. It is unknown whether lactate contributes to energy metabolism in living tumors. We previously reported that human non-small-cell lung cancers (NSCLCs) oxidize glucose in the tricarboxylic acid (TCA) cycle. Here, we show that lactate is also a TCA cycle carbon source for NSCLC. In human NSCLC, evidence of lactate utilization was most apparent in tumors with high 18fluorodeoxyglucose uptake and aggressive oncological behavior. Infusing human NSCLC patients with 13C-lactate revealed extensive labeling of TCA cycle metabolites. In mice, deleting monocarboxylate transporter-1 (MCT1) from tumor cells eliminated lactate-dependent metabolite labeling, confirming tumor-cell-autonomous lactate uptake. Strikingly, directly comparing lactate and glucose metabolism in vivo indicated that lactate's contribution to the TCA cycle predominates. The data indicate that tumors, including bona fide human NSCLC, can use lactate as a fuel in vivo.

Metabolic Heterogeneity in Human Lung Tumors.

Non-small cell lung cancer (NSCLC) is heterogeneous in the genetic and environmental parameters that influence cell metabolism in culture. Here, we assessed the impact of these factors on human NSCLC metabolism in vivo using intraoperative (13)C-glucose infusions in nine NSCLC patients to compare metabolism between tumors and benign lung. While enhanced glycolysis and glucose oxidation were common among these tumors, we observed evidence for oxidation of multiple nutrients in each of them, including lactate as a potential carbon source. Moreover, metabolically heterogeneous regions were identified within and between tumors, and surprisingly, our data suggested potential contributions of non-glucose nutrients in well-perfused tumor areas. Our findings not only demonstrate the heterogeneity in tumor metabolism in vivo but also highlight the strong influence of the microenvironment on this feature.

Contrast Media-driven Anthropogenic Gadolinium: Knowns and Unknowns.

Gadolinium-based contrast agents (GBCAs) have augmented the capabilities of MRI, which has led to their widespread and increasing use in radiology practice. GBCAs are introduced into the environment through disposal of unused product and elimination after intravenous injection, both primarily via liquid dispersion into the environment. This human introduction of gadolinium into the environment, referred to as anthropogenic gadolinium, is associated with the detection of gadolinium in water systems, raising concerns for potential adverse impact and prompting certain mitigation actions. This article summarizes the existing knowledge and problem scope, conveys the relevant underlying chemical principles of chelate dissociation, and offers an inferred perspective that the magnitude of the problem is most unlikely to cause human harm. The merits and limitations regarding possible mitigation tactics, such as collecting urine after GBCA administration, use of lower-dose high-relaxivity macrocyclic GBCAs, and the option for virtual contrast-enhanced examinations, will be discussed. Finally, the potential for monitoring gadolinium uptake in bone will be presented, and recommendations for future research will be offered. © RSNA, 2024 See also the article by Ibrahim et al in this issue. See also the article by McKee et al in this issue.

Combining inhomogeneous magnetization transfer and multipoint Dixon acquisition: Potential utility and evaluation.

PURPOSE: The recently introduced inhomogeneous magnetization transfer (ihMT) method has predominantly been applied for imaging the central nervous system. Future applications of ihMT, such as in peripheral nerves and muscles, will involve imaging in the vicinity of adipose tissues. This work aims to systematically investigate the partial volume effect of fat on the ihMT signal and to propose an efficient fat-separation method that does not interfere with ihMT measurements. METHODS: First, the influence of fat on ihMT signal was studied using simulations. Next, the ihMT sequence was combined with a multi-echo Dixon acquisition for fat separation. The sequence was tested in 9 healthy volunteers using a 3T human scanner. The ihMT ratio (ihMTR) values were calculated in regions of interest in the brain and the spinal cord using standard acquisition (no fat saturation), water-only, in-phase, and out-of-phase reconstructions. The values obtained were compared with a standard fat suppression method, spectral presaturation with inversion recovery. RESULTS: Simulations showed variations in the ihMTR values in the presence of fat, depending on the TEs used. The IhMTR values in the brain and spinal cord derived from the water-only ihMT multi-echo Dixon images were in good agreement with values from the unsuppressed sequence. The ihMT-spectral presaturation with inversion recovery combination resulted in 24%-35% lower ihMTR values compared with the standard non-fat-suppressed acquisition. CONCLUSION: The presence of fat within a voxel affects the ihMTR calculations. The IhMT multi-echo Dixon method does not compromise the observable ihMT effect and can potentially be used to remove fat influence in ihMT.

Investigating new CT contrast agents: a phantom study exploring quantification and differentiation methods for high-Z elements using dual-energy CT.

OBJECTIVES: To develop a dual-energy CT method for differentiating and quantifying high-Z contrast elements and to evaluate the limitations based on element concentration and atomic number by using an anthropomorphic phantom study. METHODS: Mass spectrometry standards for iodine, barium, gadolinium, ytterbium, tantalum, gold, and bismuth were diluted from 10.0 to 0.3 mg/mL, placed inside 7-mL vials, and scanned with dual-energy CT using an abdominal phantom and cylindrical water-filled insert. This procedure was repeated with all seven high-Z elements at six isoattenuating values from 250 to 8 HU. Quantification accuracy was measured using a linear regression model and residual error analysis with 90% limits of agreement. The limit of detection for each element was evaluated using the limit of blank of water. Pairwise differentiation of isoattenuating vials was evaluated using AUC values and the difference in fit angles between the two elements. RESULTS: Each high-Z element had a unique concentration vector in a two-dimensional plot of Compton scattering versus photoelectric effect attenuations. Mean quantification values were within ± 0.1 mg/mL of the true values for each element with no proportional bias. Limits of detection ranged from 0.35 to 0.56 mg/mL. Pairwise differentiations were proportional to the isoattenuating HU and the angle between the linear fits with mean AUC values increasing from 0.61 to 0.98 at 8 to 250 HU, respectively. CONCLUSION: Dual-energy CT can differentiate and quantify isoattenuating high-Z elements. The high-attenuation characteristics and unique concentration vectors of ytterbium, tantalum, gold, and bismuth are well suited for new dual-energy CT contrast agents especially when simultaneously imaged with iodine, barium, or gadolinium. KEY POINTS: • Dual-energy CT can accurately quantify high-Z contrast elements and readily differentiate iodine, barium, and gadolinium from ytterbium, tantalum, gold, and bismuth. • The differentiation and quantification capabilities for high-Z contrast elements are largely unaffected by phantom size and transaxial location within the phantom. • Potential benefits of new CT contrast agents based on these high-Z elements include alternatives for patients with iodine sensitivity, high conspicuity at both 120 and 140 kVp, simultaneous imaging of two contrast agents, and reduced injection volume.

How the Chemical Properties of GBCAs Influence Their Safety Profiles In Vivo.

The extracellular class of gadolinium-based contrast agents (GBCAs) is an essential tool for clinical diagnosis and disease management. In order to better understand the issues associated with GBCA administration and gadolinium retention and deposition in the human brain, the chemical properties of GBCAs such as relative thermodynamic and kinetic stabilities and their likelihood of forming gadolinium deposits in vivo will be reviewed. The chemical form of gadolinium causing the hyperintensity is an open question. On the basis of estimates of total gadolinium concentration present, it is highly unlikely that the intact chelate is causing the T1 hyperintensities observed in the human brain. Although it is possible that there is a water-soluble form of gadolinium that has high relaxitvity present, our experience indicates that the insoluble gadolinium-based agents/salts could have high relaxivities on the surface of the solid due to higher water access. This review assesses the safety of GBCAs from a chemical point of view based on their thermodynamic and kinetic properties, discusses how these properties influence in vivo behavior, and highlights some clinical implications regarding the development of future imaging agents.

MRI of the Placenta Accreta Spectrum (PAS) Disorder: Radiomics Analysis Correlates With Surgical and Pathological Outcome.

BACKGROUND: Placenta accreta spectrum (PAS) in women with previous cesarean delivery has become increasingly prevalent. Depending on the severity, patient management may involve cesarean hysterectomy. PURPOSE: To investigate textural analyses as the radiomics in MRI of the placenta in predicting the PAS requiring cesarean hysterectomy in a high-risk population. STUDY TYPE: Retrospective. POPULATION: Sixty-two women with prior cesarean delivery referred for MRI because of sonographic suspicion for PAS. FIELD STRENGTH/SEQUENCE: 1.5T with T1 W, T2 W, and diffusion-weighted imaging (DWI). ASSESSMENT: Two reviewers independently evaluated MR images based on five established PAS variables. Placental regions of interest (ROIs) were generated on T2 W, DWI, and an apparent diffusion coefficient (ADC) map, based on definitions of areas of placenta in proximity to and remote from previous surgical incision sites. STATISTICAL TESTS: Reader agreement was assessed by simple kappa and prevalence adjusted bias adjusted kappa (PABAK). T-tests and chi-square analyses between the primary outcome (hysterectomy vs. no hysterectomy) were performed. Thirteen Haralick texture features calculated from gray-level co-occurrence matrixes were extracted from manually drawn placental ROIs within each of three MR acquisitions. Univariate and multivariable logistic regression were used to assess the association with cesarean hysterectomy. RESULTS: Of 62 pregnancies at risk for PAS, 40 required cesarean hysterectomy (65%), with excellent correlation between need for hysterectomy and pathology confirmation of PAS in the hysterectomy specimen [κ = 0.82 (0.62, 1)]. Reader agreement was fair to moderate. Of the 13 Haralick variables within each of three acquisition groups, significant differences (P < 0.05) were seen in 22 of 39 parameters comparing placental ROIs in proximity to incision scar(s) to those ROIs remote from scar. A stepwise selection algorithm indicated that the combination of T2 W Fcm.sum.var , ADC Fcm.diff.entr , and DWI Fcm.energy gave the highest leave-one-out-AUC of 0.80 (0.68, 0.91). DATA CONCLUSION: Assessment of PAS severity is subjective and dependent on radiologist expertise. We identified textural features on placental MR images in the region of the prior uterine scar that differentiated pregnancies requiring cesarean hysterectomy based on clinical suspicion of PAS from those that did not, suggesting predictive capabilities of these objective radiomics features. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:936-946.

A Technique to Identify Isoattenuating Gallstones with Dual-Layer Spectral CT: An ex Vivo Phantom Study.

Background Previously reported dual-energy CT methods for detecting noncalcified gallstones have reduced accuracy for gallstones smaller than 9 mm. Purpose To develop a dual-energy CT method for differentiating isoattenuating gallstones from bile and compare it with previously reported dual-energy CT methods by using a prospective ex vivo phantom reader study. Materials and Methods From May 2017 to May 2018, gallstones were collected from 105 patients (34 men; mean age, 51 years; age range, 18-84 years) undergoing cholecystectomy and placed inside 120-mL vials containing ox bile. The vials were placed inside a water-filled phantom and were scanned with dual-layer dual-energy CT. Thirty isoattenuating gallstones (4.3-24.7 mm in diameter) were evaluated. Conventional CT images, virtual noncontrast images, and monoenergetic images at 200 and 40 keV were created. Segmented images were created by using a two-dimensional histogram of Compton and photoelectric attenuation. Six readers evaluated the presence of isoattenuating gallstones in each image. Intra- and interreader agreement was measured by using percentage agreement, diagnostic performance was evaluated by using mean area under the receiver operating characteristic curve (AUC) estimates and pairwise comparisons, and the agreement of gallstone sizes measured at pathologic examination with those measured on segmented images was compared by using Bland-Altman analysis. Results For all gallstones, segmented images provided the highest mean intrareader (88.1%) and interreader (88.2% and 93.6%) agreements for all readers and reading sessions and the highest overall AUC (0.99; 95% confidence interval [CI]: 0.97, 1.00; adjusted P < .02 for all). For gallstones larger than 9 mm, no significant difference was found between the segmented and monoenergetic AUCs (all P > .94, adjusted P > .05 for all). For gallstones measuring 9 mm or smaller, the segmented images had the highest overall AUC (0.99; 95% CI: 0.97, 1.00; adjusted P < .01 for all). The mean difference in stone sizes was -0.6 mm, with limits of agreement from 2.6 to -3.8 mm. Conclusion Segmented images from Compton and photoelectric attenuation coefficients improve detection of isoattenuating gallstones compared with previously reported dual-energy CT methods. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Matos in this issue.

Accelerating chemical exchange saturation transfer MRI with parallel blind compressed sensing.

PURPOSE: Chemical exchange saturation transfer is a novel and promising MRI contrast method, but it can be time-consuming. Common parallel imaging methods, like SENSE, can lead to reduced quality of CEST. Here, parallel blind compressed sensing (PBCS), combining blind compressed sensing (BCS) and parallel imaging, is evaluated for the acceleration of CEST in brain and breast. METHODS: The CEST data were collected in phantoms, brain (N = 3), and breast (N = 2). Retrospective Cartesian undersampling was implemented and the reconstruction results of PBCS-CEST were compared with BCS-CEST and k-t sparse-SENSE CEST. The normalized RMSE and the high-frequency error norm were used for quantitative comparison. RESULTS: In phantom and in vivo brain experiments, the acceleration factor of R = 10 (24 k-space lines) was achieved and in breast R = 5 (30 k-space lines), without compromising the quality of the PBCS-reconstructed magnetization transfer rate asymmetry maps and Z-spectra. Parallel BCS provides better reconstruction quality when compared with BCS, k-t sparse-SENSE, and SENSE methods using the same number of samples. Parallel BCS overperforms BCS, indicating that the inclusion of coil sensitivity improves the reconstruction of the CEST data. CONCLUSION: The PBCS method accelerates CEST without compromising its quality. Compressed sensing in combination with parallel imaging can provide a valuable alternative to parallel imaging alone for accelerating CEST experiments.

Gadolinium Retention: A Research Roadmap from the 2018 NIH/ACR/RSNA Workshop on Gadolinium Chelates.

Gadolinium-based contrast agents (GBCAs) have revolutionized MRI, enabling physicians to obtain crucial life-saving medical information that often cannot be obtained with other imaging modalities. Since initial approval in 1988, over 450 million intravenous GBCA doses have been administered worldwide, with an extremely favorable pharmacologic safety profile; however, recent information has raised new concerns over the safety of GBCAs. Mounting evidence has shown there is long-term retention of gadolinium in human tissues. Further, a small subset of patients have attributed a constellation of symptoms to GBCA exposure, although the association of these symptoms with GBCA administration or gadolinium retention has not been proven by scientific investigation. Despite evidence that macrocyclic GBCAs show less gadolinium retention than linear GBCAs, the safety implications of gadolinium retention are unknown. The mechanism and chemical forms of gadolinium retention, as well as the biologic activity and clinical importance of these retained gadolinium species, remain poorly understood and underscore the need for additional research. In February 2018, an international meeting was held in Bethesda, Md, at the National Institutes of Health to discuss the current literature and knowledge gaps about gadolinium retention, to prioritize future research initiatives to better understand this phenomenon, and to foster collaborative standardized studies. The greatest priorities are to determine (a) if gadolinium retention adversely affects the function of human tissues, (b) if retention is causally associated with short- or long-term clinical manifestations of disease, and (c) if vulnerable populations, such as children, are at greater risk for experiencing clinical disease. The purpose of the research roadmap is to highlight important information that is not known and to identify and prioritize needed research. ©RSNA, 2018 Online supplemental material is available for this article .

Z-spectrum appearance and interpretation in the presence of fat: Influence of acquisition parameters.

PURPOSE: Chemical exchange saturation transfer (CEST) MRI is increasingly evolving from brain to body applications. One of the known problems in the body imaging is the presence of strong lipid signals. Although their influence on the CEST effect is acknowledged, there was no study that focuses on the interplay among echo time, fat fraction, and Z-spectrum. This study strives to address these points, with the emphasis on the application in the breast. METHODS: Z-spectra were simulated in phase and out of phase of the main fat peak at -3.4 ppm, with the fat fraction varying from 0 to 100%. The magnetization transfer ratio asymmetry in two ranges, centering at the exchanging pool and at 3.5 ppm approximately opposite the nonexchanging fat pool, were calculated and were plotted against fat fraction. The results were verified in phantoms and in vivo. RESULTS: The results demonstrate the combined influence of fat fraction and echo time on the Z-spectrum for gradient echo based CEST acquisitions. The influence is straightforward in the in-phase images, but it is more complicated in the out-of-phase images, potentially leading to erroneous CEST contrast. CONCLUSIONS: This study provides a basis for understanding the origin and appearance of lipid artifacts in CEST imaging, and lays the foundation for their efficient removal. Magn Reson Med 79:2731-2737, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Whole-body MRI for metastatic cancer detection using T2 -weighted imaging with fat and fluid suppression.

PURPOSE: To develop a whole-body MRI technique at 3T with improved lesion conspicuity for metastatic cancer detection using fast, high-resolution and high SNR T2 -weighted (T2 W) imaging with simultaneous fat and fluid suppression. THEORY AND METHODS: The proposed dual-echo T2 -weighted acquisition for enhanced conspicuity of tumors (DETECT) acquires 4 images, in-phase (IP) and out-of-phase (OP) at a short and a long TE using single-shot turbo spin echo. The IP/OP images at the short and long TEs are reconstructed using the standard Dixon and shared-field-map Dixon reconstruction respectively, for robust fat-water separation. An adaptive complex subtraction between the 2 TE water-only images achieves fluid attenuation. DETECT imaging was optimized and evaluated in whole-body imaging of 5 healthy volunteers, and compared against diffusion-weighted imaging with background suppression (DWIBS) in 5 patients with known metastatic renal cell carcinoma. RESULTS: Robust fat-water separation and fluid attenuation were achieved using the shared-field-map Dixon reconstruction and adaptive complex subtraction, respectively. DETECT imaging technique generated co-registered T2 W images with and without fat suppression, heavily T2 W, and fat and fluid suppressed T2 W whole-body images in <7 min. Compared to DWIBS acquired in 17 min, the DETECT imaging achieved better detection and localization of lesions in patients with metastatic cancer. CONCLUSION: DETECT imaging technique generates T2 W images with high resolution, high SNR, minimal geometric distortions, and provides good lesion conspicuity with robust fat and fluid suppression in <7 min for whole-body imaging, demonstrating efficient and reliable metastatic cancer detection at 3T.

Microstructural correlates of 3D steady-state inhomogeneous magnetization transfer (ihMT) in the human brain white matter assessed by myelin water imaging and diffusion tensor imaging.

PURPOSE: To compare the recently introduced inhomogeneous magnetization transfer (ihMT) technique with more established MRI techniques including myelin water imaging (MWI) and diffusion tensor imaging (DTI), and to evaluate the microstructural attributes correlating with this new contrast method in the human brain white matter. METHODS: Eight adult healthy volunteers underwent T1 -weighted, ihMT, MWI, and DTI imaging on a 3T human scanner. The ihMT ratio (ihMTR), myelin water fraction (MWF), fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) values were calculated from different white matter tracts. The angle ( θ ) between the directions of the principal eigenvector, as measured by DTI, and the main magnetic field was calculated for all voxels from various fiber tracts. The ihMTR was correlated with MWF and DTI metrics. RESULTS: A strong correlation was found between ihMTR and MWF (ρ = 0.77, P < 0.0001). This was followed by moderate to weak correlations between ihMTR and DTI metrics: RD (ρ = -0.30, P < 0.0001), FA (ρ = 0.20, P < 0.0001), MD (ρ = -0.19, P < 0.0001), AD (ρ = 0.02, P < 0.0001). A strong correlation was found between ihMTR and θ (ρ = -0.541, P < 0.0001). CONCLUSION: The strong correlation with myelin water imaging and its low coefficient of variation suggest that ihMT has the potential to become a new structural imaging marker of myelin. The substantial orientational dependence of ihMT should be taken into account when evaluating and quantitatively interpreting ihMT results.

Phantom Validation of Spectral Detector Computed Tomography-Derived Virtual Monoenergetic, Virtual Noncontrast, and Iodine Quantification Images.

PURPOSE: Spectral detector computed tomography (SDCT) is a new CT technology that uses a dual-layer detector to perform energy separation. We aim to assess 3 clinical concepts using a phantom model: noise profile across the virtual monoenergetic (VME) spectrum, accuracy of iodine quantification, and virtual noncontrast (VNC) reconstructions' ability to remove iodine contribution to attenuation. METHODS: Six vials containing varying concentrations of iodinated contrast (0-6 mg/mL) diluted in water were placed in a water bath and scanned on an SDCT scanner. Virtual monoenergetic (40-200 keV at 10-keV increments), iodine-no-water, and VNC reconstructions were created. Attenuation (in Hounsfield units [HU]), VME noise at each energy level, CT-derived iodine concentration, and VNC attenuation were recorded. RESULTS: Virtual monoenergetic noise was improved at all energies compared with conventional images (conventional, 9.8-11.2; VME, 7.5-9.5). Noise profile showed a slightly higher image noise at 40 keV, but was otherwise relatively flat across the energy spectrum. On iodine-no-water reconstructions, measured varied from actual iodine concentration by ±0.1 mg/mL (SD, 0.16-0.36). Virtual noncontrast attenuation was within 5 HU of water attenuation at all iodine concentrations. CONCLUSION: Reconstructions of SDCT show lower VME image noise, accurate iodine quantification, and VNC attenuation values within 5 HU of expected in a phantom model.

MR Neurography of Brachial Plexus at 3.0 T with Robust Fat and Blood Suppression.

Purpose To develop and evaluate magnetic resonance (MR) neurography of the brachial plexus with robust fat and blood suppression for increased conspicuity of nerves at 3.0 T in clinically feasible acquisition times. Materials and Methods This prospective study was HIPAA compliant, with institutional review board approval and written informed consent. A low-refocusing-flip-angle three-dimensional (3D) turbo spin-echo (TSE) sequence was modified to acquire both in-phase and out-of-phase echoes, required for chemical shift (Dixon) reconstruction, in the same repetition by using partial echoes combined with modified homodyne reconstruction with phase preservation. This multiecho TSE modified Dixon (mDixon) sequence was optimized by using simulations and phantom studies and in three healthy volunteers. The sequence was tested in five healthy volunteers and was evaluated in 10 patients who had been referred for brachial plexopathy at 3.0 T. The images were evaluated against the current standard of care, images acquired with a 3D TSE short inversion time inversion recovery (STIR) sequence, qualitatively by using the Wilcoxon signed-rank test and quantitatively by using the Friedman two-way analysis of variance, with P < .05 considered to indicate a statistically significant difference. Results Multiecho TSE-mDixon involving partial-echo and homodyne reconstruction with phase preservation achieved uniform fat suppression in half the imaging time compared with multiacquisition TSE-mDixon. Compared with 3D TSE STIR, fat suppression, venous suppression, and nerve visualization were significantly improved (P < .05), while arterial suppression was better but not significantly so (P = .06), with increased apparent signal-to-noise ratio in the dorsal nerve root ganglion and C6 nerve (P < .001) with the multiecho TSE-mDixon sequence. Conclusion The multiecho 3D TSE-mDixon sequence provides robust fat and blood suppression, resulting in increased conspicuity of the nerves, in clinically feasible imaging times and can be used for MR neurography of the brachial plexus at 3.0 T. © RSNA, 2016 Online supplemental material is available for this article.

Quantitative diffusion-weighted imaging and dynamic contrast-enhanced characterization of the index lesion with multiparametric MRI in prostate cancer patients.

PURPOSE: To compare a simplified intravoxel incoherent motion (sIVIM) model to commonly used monoexponential and biexponential models in the characterization of prostate cancer (PCa) and noncancerous prostate tissues, and to investigate combinations of diffusion-weighted imaging (DWI) measures with dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI)-derived parameters in MRI-visible index lesions, to facilitate PCa risk stratification. MATERIALS AND METHODS: In this retrospective, Institutional Review Board (IRB)-approved study, 43 consecutive patients with PCa who had 3T MRI exams followed by radical prostatectomy were included. DWI and DCE parameters were measured from one index lesion per patient, and noncancerous central gland and peripheral zone. Logistic regression modeling was performed to select the optimal combination of DWI and DCE measurements for tumor risk assessment. RESULTS: All diffusion models showed the lowest diffusion coefficients in tumors, intermediate values in noncancerous central gland, and highest values in noncancerous peripheral zone (all P < 0.001). Ktrans and kep were higher in tumors compared to central gland (P < 0.005) and peripheral zone (P < 0.001). The initial area under the contrast concentration curve was higher in tumor than the peripheral zone (P < 0.001). The area under the receiver operating characteristic curve of the combined DWI and DCE parameters (0.78) was higher than its individual components (0.73 and 0.63, respectively) for discriminating low- and intermediate-to-high-risk tumors. CONCLUSION: The sIVIM model provided comparable results with fewer b-values and shorter image acquisition time. The combination of DWI and DCE measurements of MRI-visible index lesions improved the preoperative prostate cancer risk characterization compared to the individual parameters from either technique alone. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:908-916.

UCEPR: Ultrafast localized CEST-spectroscopy with PRESS in phantoms and in vivo.

PURPOSE: Chemical exchange saturation transfer (CEST) is a contrast mechanism enhancing low-concentration molecules through saturation transfer from their exchangeable protons to bulk water. Often many scans are acquired to form a Z-spectrum, making the CEST method time-consuming. Here, an ultrafast localized CEST-spectroscopy with PRESS (UCEPR) is proposed to obtain the entire Z-spectrum of a voxel using only two scans, significantly accelerating CEST. THEORY AND METHODS: The approach combines ultrafast nonlocalized CEST spectroscopy with localization using PRESS. A field gradient is applied concurrently with the saturation pulse producing simultaneous saturation of all Z-spectrum frequencies that are also spatially encoded. A readout gradient during data acquisition resolves the spatial dependence of the CEST responses into frequency. UCEPR was tested on a 3T scanner both in phantoms and in vivo. RESULTS: In phantoms, a fast Z-spectroscopy acquisition of multiple pH-variant iopamidol samples was achieved with four- to seven-fold acceleration as compared to the conventional CEST methods. In vivo, amide proton transfer (APT) in white matter of healthy human brain was measured rapidly in 48 s and with high frequency resolution (≤ 0.2 ppm). CONCLUSION: Compared with conventional CEST methods, UCEPR has the advantage of rapidly acquiring high-resolution Z-spectra. Potential in vivo applications include ultrafast localized Z-spectroscopy, quantitative, or dynamic CEST studies.

pH imaging of mouse kidneys in vivo using a frequency-dependent paraCEST agent.

PURPOSE: This study explored the feasibility of using a pH responsive paramagnetic chemical exchange saturation transfer (paraCEST) agent to image the pH gradient in kidneys of healthy mice. METHODS: CEST signals were acquired on an Agilent 9.4 Tesla small animal MRI system using a steady-state gradient echo pulse sequence after a bolus injection of agent. The magnetic field inhomogeneity across each kidney was corrected using the WASSR method and pH maps were calculated by measuring the frequency of water exchange signal arising from the agent. RESULTS: Dynamic CEST studies demonstrated that the agent was readily detectable in kidneys only between 4 to 12 min postinjection. The CEST images showed a higher signal intensity in the pelvis and calyx regions and lower signal intensity in the medulla and cortex regions. The pH maps reflected tissue pH values spanning from 6.0 to 7.5 in kidneys of healthy mice. CONCLUSION: This study demonstrated that pH maps of the kidney can be imaged in vivo by measuring the pH-dependent chemical shift of a single water exchange CEST peak without prior knowledge of the agent concentration in vivo. The results demonstrate the potential of using a simple frequency-dependent paraCEST agent for mapping tissue pH in vivo. Magn Reson Med 75:2432-2441, 2016. © 2015 Wiley Periodicals, Inc.

Selective spectroscopic imaging of hyperpolarized pyruvate and its metabolites using a single-echo variable phase advance method in balanced SSFP.

PURPOSE: In balanced steady state free precession (bSSFP), the signal intensity has a well-known dependence on the off-resonance frequency, or, equivalently, the phase advance between successive radiofrequency (RF) pulses. The signal profile can be used to resolve the contributions from the spectrally separated metabolites. This work describes a method based on use of a variable RF phase advance to acquire spatial and spectral data in a time-efficient manner for hyperpolarized 13C MRI. THEORY AND METHODS: The technique relies on the frequency response from a bSSFP acquisition to acquire relatively rapid, high-resolution images that may be reconstructed to separate contributions from different metabolites. The ability to produce images from spectrally separated metabolites was demonstrated in vitro, as well as in vivo following administration of hyperpolarized 1-13C pyruvate in mice with xenograft tumors. RESULTS: In vivo images of pyruvate, alanine, pyruvate hydrate, and lactate were reconstructed from four images acquired in 2 s with an in-plane resolution of 1.25 × 1.25 mm(2) and 5 mm slice thickness. CONCLUSION: The phase advance method allowed acquisition of spectroscopically selective images with high spatial and temporal resolution. This method provides an alternative approach to hyperpolarized 13C spectroscopic MRI that can be combined with other techniques such as multiecho or fluctuating equilibrium bSSFP. Magn Reson Med 76:1102-1115, 2016. © 2015 Wiley Periodicals, Inc.