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Purpose A standard MRI system phantom has been designed and fabricated to assess scanner performance, stability, comparability and assess the accuracy of quantitative relaxation time imaging. The phantom is unique in having traceability to the International System of Units, a high level of precision, and monitoring by a national metrology institute. Here, we describe the phantom design, construction, imaging protocols, and measurement of geometric distortion, resolution, slice profile, signal-to-noise ratio (SNR), proton-spin relaxation times, image uniformity and proton density. Methods The system phantom, designed by the International Society of Magnetic Resonance in Medicine ad hoc committee on Standards for Quantitative MR, is a 200 mm spherical structure that contains a 57-element fiducial array; two relaxation time arrays; a proton density/SNR array; resolution and slice-profile insets. Standard imaging protocols are presented, which provide rapid assessment of geometric distortion, image uniformity, T1 and T2 mapping, image resolution, slice profile, and SNR. Results Fiducial array analysis gives assessment of intrinsic geometric distortions, which can vary considerably between scanners and correction techniques. This analysis also measures scanner/coil image uniformity, spatial calibration accuracy, and local volume distortion. An advanced resolution analysis gives both scanner and protocol contributions. SNR analysis gives both temporal and spatial contributions. Conclusions A standard system phantom is useful for characterization of scanner performance, monitoring a scanner over time, and to compare different scanners. This type of calibration structure is useful for quality assurance, benchmarking quantitative MRI protocols, and to transition MRI from a qualitative imaging technique to a precise metrology with documented accuracy and uncertainty.

The MRI community is using quantitative mapping techniques to complement qualitative imaging. For quantitative imaging to reach its full potential, it is necessary to analyze measurements across systems and longitudinally. Clinical use of quantitative imaging can be facilitated through adoption and use of a standard system phantom, a calibration/standard reference object, to assess the performance of an MRI machine. The International Society of Magnetic Resonance in Medicine AdHoc Committee on Standards for Quantitative Magnetic Resonance was established in February 2007 to facilitate the expansion of MRI as a mainstream modality for multi-institutional measurements, including, among other things, multicenter trials. The goal of the Standards for Quantitative Magnetic Resonance committee was to provide a framework to ensure that quantitative measures derived from MR data are comparable over time, between subjects, between sites, and between vendors. This paper, written by members of the Standards for Quantitative Magnetic Resonance committee, reviews standardization attempts and then details the need, requirements, and implementation plan for a standard system phantom for quantitative MRI. In addition, application-specific phantoms and implementation of quantitative MRI are reviewed. Magn Reson Med 79:48-61, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

The MRI community is using quantitative mapping techniques to complement qualitative imaging. For quantitative imaging to reach its full potential, it is necessary to analyze measurements across systems and longitudinally. Clinical use of quantitative imaging can be facilitated through adoption and use of a standard system phantom, a calibration/standard reference object, to assess the performance of an MRI machine. The International Society of Magnetic Resonance in Medicine AdHoc Committee on Standards for Quantitative Magnetic Resonance was established in February 2007 to facilitate the expansion of MRI as a mainstream modality for multi-institutional measurements, including, among other things, multicenter trials. The goal of the Standards for Quantitative Magnetic Resonance committee was to provide a framework to ensure that quantitative measures derived from MR data are comparable over time, between subjects, between sites, and between vendors. This paper, written by members of the Standards for Quantitative Magnetic Resonance committee, reviews standardization attempts and then details the need, requirements, and implementation plan for a standard system phantom for quantitative MRI. In addition, application-specific phantoms and implementation of quantitative MRI are reviewed. Magn Reson Med 79:48-61, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

MRI-based cartilage morphometry was previously validated in the absence of gadopentate dimeglumine (Gd-DTPA). However, Gd-DTPA is required for compositional (proteoglycan) imaging using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). Therefore, the effect of Gd-DTPA on cartilage morphometry was studied. A total of 165 female participants (67 with and 98 without osteoarthritis [OA]) were imaged at 3.0 Tesla before and 2 hr after intravenous Gd-DTPA injection. Flip angles in post-Gd-DTPA scans varied between 12° and 35°. Cartilage volume and thickness of post- vs. pre-Gd-DTPA scans showed intraclass correlation coefficients (ICCs) of 0.85 ≥ r ≥ 0.95, mean differences between –2.1% and +1.1%, and standard deviations (SDs) of differences between 4.7% and 9.2%. Mixed-effect models found no consistent impact of flip angle and OA status on post- vs. pre-Gd-DTPA differences. Accurate morphological measurements of cartilage can be obtained after Gd-DTPA injection, allowing compositional and morphological imaging to be combined into one session. Magn Reson Med 58:402–406, 2007. © 2007 Wiley-Liss, Inc.

Whole-volume tumor perfusion measured using nuclear magnetic resonance (NMR) observation of deuterated water uptake after intravenous injection and a common arterial input function (AIF) derived from AIF estimates in a small set of animals was compared with perfusion measured by the commonly used microsphere method in rat 9L gliosarcomas. Tumor perfusion estimated with this optimized NMR technique using an appropriate common AIF (i.e., taking into account the duration of anesthesia) correlates highly (n 5 13, P 5 0.001) with that measured by the microsphere method, yielding no significant differences (P 5 0.5, paired Student’s t-test). Thus, the optimized NMR method can be used for repeatable, non-invasive, and quantitative measurements of tumor perfusion. Magn Reson Med 42:240‐247, 1999. r 1999 Wiley-Liss, Inc.

This paper considers potential problems encountered when using the Kety approach to measure perfusion in small laboratory animals with nuclear magnetic resonance (NMR) tracer uptake methods: a) the need to measure the arterial input function (AIF) in each animal; b) sensitivity to perfusion heterogeneity; c) sensitivity to low signal-to-noise ratio (SNR); and d) influence of changes in the AIF. A method to estimate the AIF in rats is presented that derives an AIF from the time course of a tracer passing through a carotid chamber. The results of computer simulations indicate that a common AIF obtained in one set of animals can be used for perfusion estimations in another set of animals if the tracer is delivered as a dose and that optimal data analysis (fitting data vs. integration approach) is dictated by SNR and perfusion heterogeneity. Experimental strategies are suggested to minimize the effects of changes in the individual AIF that could distort perfusion estimates.

The principal aim of these studies was to evaluate the utility of isoflurane and halothane for NMR investigations of tumor physiology. In vivo 31 P and 2 H NMR were used to examine RIF-1 tumors before, during, and (for 31 P) after anesthesia. In tumors, halothane decreases blood flow, [PCR]:[NTP], and pH indicated by the P i chemical shift (pH nmr ), while it increases [P i ]:[NTP]; effects consistent with well-established cardiovascular effects of halothane. Isoflurane does not affect tumor blood flow or [PCr]:[NTP], but increases tumor [P i ]:[NTP] and decreases tumor pH nmr . In vivo 31 P NMR measurements of normal mouse liver (upper abdomen) indicate that isoflurane has a similar effect in the liver. Although the mechanism for these effects is unknown, observation of a split P i peak during isoflurane anesthesia suggests that a pool of P i in a lower pH environment may become evident under isoflurane anesthesia. Regardless of the cause for increased [P i ]:[NTP] and decreased pH nmr , the utility of isoflurane anesthesia for 31 P NMR studies of energy metabolism is limited

A noninvasive method to measure relative regional tumor blood flow (rTBF) throughout murine tumors which uses deuterium NMR imaging to observe regional uptake of HOD after bolus iv injection of D2O is introduced. HOD uptake images are formed by subtraction of a background (preinjection) image from 94-s gradient-refocused deuterium NMR images acquired starting 30 s and 10 min after D2O injection. The pixel intensity in the HOD uptake image acquired starting 30 s after injection is directly related to rTBF with a limit of detection estimated at 7 ml/(100 g-min). The image acquired 10 min after D2O injection extends the estimated limit of detection for rTBF to 3 ml/(100 g-min). Heterogeneity in rTBF and regional effects of photodynamic therapy within RIF-1 tumors are readily perceived. This method may provide a valuable tool to further our understanding of the relationship between blood flow and therapeutic response in tumors. © 1992 Academic Press, Inc.

A standard differential calculus-based propagation of error treatment is applied to the traditional chemical-exchange Henderson-Hasselbalch NMR pH model in which the reference shift is pH independent. It is seen naturally from this analysis that (i) the error minimum in derived pH occurs in the region where pH and indicator pK a are equal and that (ii) the dynamic range, or difference between the limiting chemical shifts of acid and base forms of indicator species, determines the insensitivity of the technique to propagation of errors. To extend the useful pH range and utility of NMR pH determination methodology, a more general model is developed in which the internal reference species is also considered as having a pH-dependent chemical shift. Data from standard solution pH titrations are fitted to both models and parameters are estimated for the normally observed family of ionizable phosphorus metabolites (ATP, inorganic phosphate, phosphoethanolamine and phosphocholine) and the xenometabolite 2-deoxyglucose-6-phosphate with either phosphocreatine, the α-phosphate of ATP, or H 2 O taken as the 31 P or 1 H chemical shift internal reference species as well as with an external reference.

Uncertainty regarding the intracellular/extracellular distribution of inorganic phosphate (P(i)) in tumors has raised concerns that pH calculated from the tumor P(i) chemical shift may not accurately represent the intracellular pH (pHin). This issue was addressed in subcutaneously transplanted murine radiation induced fibrosarcoma-1 by directly comparing pH measured via P(i) with pH measured via the in situ generated intracellular xenometabolite 2-deoxyglucose-6-phosphate (2DG6P). In 131 comparative measurements employing eight tumor-bearing mice under both control and hyperglycemic conditions (the latter to extend the range of tumor pH examined), the pH as derived from either 2DG6P or P(i) showed only a small, but statistically significant, difference (0.07 +/- 0.11 SD; P = 0.0001). Scatter in the comparative analysis over the pH range examined (ca. 5.5-7.5) was not uniform. Above pH 6.6, 2DG6P indicated a pH lower than that of P(i) by 0.088 +/- 0.105 SD (n = 107, P = 0.0001); below pH 6.6, 2DG6P indicated a pH essentially identical to and not statistically different from that of P(i) (mean difference 0.003 +/- 0.128 SD (n = 24, P = 0.92)). Evidence is presented in support of this differential arising from a systematic measurement error due to peak overlap between 2DG6P and endogenous phosphomonoester species. These results support the use of P(i) as a tumor 31P NMR pHin indicator, at least in RIF-1 tumors under control and hyperglycemic conditions.

A deuterium NMR spectroscopic method to determine relative tumor blood flow (TBF) by measuring the increase in tumor HOD concentration after intravenous injection of 100 μl D2O (0.9% NaCl) is presented. An integration approach analogous to that validated for positron emission tomographic measurement of cerebral blood flow was implemented. Computer simulations indicated that integration from 30 to 120 s minimizes the sensitivity of the uptake integral to the shape of the arterial input function, which cannot be assessed in each mouse, while maintaining both a nearly linear relationship between TBF and the integral and high NMR signal-to-noise. A strong positive linear correlation was observed between the uptake integral and TBF measured by D2O clearance in both untreated tumors (n = 19; P < 0.001) and tumors after hyperthermia (n = 16; P < 0.001). This method can measure relative TBF in tumors with heterogeneous blood flow and is ideally suited to concurrent or interleaved measurement of TBF and metabolism via multinuclear NMR spectroscopy. © 1991 Academic Press. Inc.

Phosphorus-31 NMR spin-lattice relaxation times and resonance linewidths of rat leg muscle, brain, and liver metabolites in vivo have been examined at 1.9-, 4.7-, and 8.5-T static magnetic field strengths. The resonance linewidths expressed in ppm that have been measured are independent of field strength. The spin-lattice relaxation times of muscle and brain phosphorus metabolites decrease linearly with increasing field strength while those of liver are constant over the range of static fields examined.

The use of 2H-labeled drugs provides a measure of drug concentration in situ directly from a single 2H NMR spectrum obtained with any antenna by correcting only for differential saturation effects. The limit of detection for a drug labeled with three equivalent deuterons is roughly 0.5 mM.