Linearity and Bias of Proton Density Fat Fraction as a Quantitative Imaging Biomarker: A Multicenter, Multiplatform, Multivendor Phantom Study.

Background Proton density fat fraction (PDFF) estimated by using chemical shift-encoded (CSE) MRI is an accepted imaging biomarker of hepatic steatosis. This work aims to promote standardized use of CSE MRI to estimate PDFF. Purpose To assess the accuracy of CSE MRI methods for estimating PDFF by determining the linearity and range of bias observed in a phantom. Materials and Methods In this prospective study, a commercial phantom with 12 vials of known PDFF values were shipped across nine U.S. centers. The phantom underwent 160 independent MRI examinations on 27 1.5-T and 3.0-T systems from three vendors. Two three-dimensional CSE MRI protocols with minimal T1 bias were included: vendor and standardized. Each vendor's confounder-corrected complex or hybrid magnitude-complex based reconstruction algorithm was used to generate PDFF maps in both protocols. The Siemens reconstruction required a configuration change to correct for water-fat swaps in the phantom. The MRI PDFF values were compared with the known PDFF values by using linear regression with mixed-effects modeling. The 95% CIs were calculated for the regression slope (ie, proportional bias) and intercept (ie, constant bias) and compared with the null hypothesis (slope = 1, intercept = 0). Results Pooled regression slope for estimated PDFF values versus phantom-derived reference PDFF values was 0.97 (95% CI: 0.96, 0.98) in the biologically relevant 0%-47.5% PDFF range. The corresponding pooled intercept was -0.27% (95% CI: -0.50%, -0.05%). Across vendors, slope ranges were 0.86-1.02 (vendor protocols) and 0.97-1.0 (standardized protocol) at 1.5 T and 0.91-1.01 (vendor protocols) and 0.87-1.01 (standardized protocol) at 3.0 T. The intercept ranges (absolute PDFF percentage) were -0.65% to 0.18% (vendor protocols) and -0.69% to -0.17% (standardized protocol) at 1.5 T and -0.48% to 0.10% (vendor protocols) and -0.78% to -0.21% (standardized protocol) at 3.0 T. Conclusion Proton density fat fraction estimation derived from three-dimensional chemical shift-encoded MRI in a commercial phantom was accurate across vendors, imaging centers, and field strengths, with use of the vendors' product acquisition and reconstruction software. © RSNA, 2021 See also the editorial by Dyke in this issue.

A standard system phantom for magnetic resonance imaging.

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.

ACR guidance document on MR safe practices: Updates and critical information 2019.

The need for a guidance document on MR safe practices arose from a growing awareness of the MR environment's potential risks and adverse event reports involving patients, equipment, and personnel. Initially published in 2002, the American College of Radiology White Paper on MR Safety established de facto industry standards for safe and responsible practices in clinical and research MR environments. The most recent version addresses new sources of risk of adverse events, increases awareness of dynamic MR environments, and recommends that those responsible for MR medical director safety undergo annual MR safety training. With regular updates to these guidelines, the latest MR safety concerns can be accounted for to ensure a safer MR environment where dangers are minimized. Level of Evidence: 1 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020;51:331-338.

Quantitative imaging biomarkers alliance (QIBA) recommendations for improved precision of DWI and DCE-MRI derived biomarkers in multicenter oncology trials.

Physiological properties of tumors can be measured both in vivo and noninvasively by diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging. Although these techniques have been used for more than two decades to study tumor diffusion, perfusion, and/or permeability, the methods and studies on how to reduce measurement error and bias in the derived imaging metrics is still lacking in the literature. This is of paramount importance because the objective is to translate these quantitative imaging biomarkers (QIBs) into clinical trials, and ultimately in clinical practice. Standardization of the image acquisition using appropriate phantoms is the first step from a technical performance standpoint. The next step is to assess whether the imaging metrics have clinical value and meet the requirements for being a QIB as defined by the Radiological Society of North America's Quantitative Imaging Biomarkers Alliance (QIBA). The goal and mission of QIBA and the National Cancer Institute Quantitative Imaging Network (QIN) initiatives are to provide technical performance standards (QIBA profiles) and QIN tools for producing reliable QIBs for use in the clinical imaging community. Some of QIBA's development of quantitative diffusion-weighted imaging and dynamic contrast-enhanced QIB profiles has been hampered by the lack of literature for repeatability and reproducibility of the derived QIBs. The available research on this topic is scant and is not in sync with improvements or upgrades in MRI technology over the years. This review focuses on the need for QIBs in oncology applications and emphasizes the importance of the assessment of their reproducibility and repeatability. Level of Evidence: 5 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;49:e101-e121.

Recommendations towards standards for quantitative MRI (qMRI) and outstanding needs.

LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019.

Quantitative magnetic resonance imaging phantoms: A review and the need for a system phantom.

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.

Prequit fMRI responses to pleasant cues and cigarette-related cues predict smoking cessation outcome.

INTRODUCTION: The reasons that some smokers find it harder to quit than others are unclear. Understanding how individual differences predict smoking cessation outcomes may allow the development of more successful personalized treatments for nicotine dependence. Theoretical models suggest that drug users might be characterized by increased sensitivity to drug cues and by reduced sensitivity to nondrug-related natural rewards. We hypothesized that baseline differences in brain sensitivity to natural rewards and cigarette-related cues would predict the outcome of a smoking cessation attempt. METHODS: Using functional magnetic resonance imaging, we recorded prequit brain responses to neutral, emotional (pleasant and unpleasant), and cigarette-related cues from 55 smokers interested in quitting. We then assessed smoking abstinence, mood, and nicotine withdrawal symptoms during the course of a smoking cessation attempt. RESULTS: Using cluster analysis, we identified 2 groups of smokers who differed in their baseline responses to pleasant cues and cigarette-related cues in the posterior visual association areas, the dorsal striatum, and the medial and dorsolateral prefrontal cortex. Smokers who showed lower prequit levels of brain reactivity to pleasant stimuli than to cigarette-related cues were less likely to be abstinent 6 months after their quit attempt, and they had higher levels of negative affect during the course of the quit attempt. CONCLUSIONS: Smokers with blunted brain responses to pleasant stimuli, relative to cigarette-related stimuli, had more difficulty quitting smoking. For these individuals, the lack of alternative forms of reinforcement when nicotine deprived might be an important factor underlying relapse. Normalizing these pathological neuroadaptations may help them achieve abstinence.

Deformable anatomic templates embed knowledge into brain images: part 2. Validation using functional magnetic resonance imaging of the motor hand.

OBJECTIVE: This study evaluated the concordance between the Deformable Anatomic Template (DAT)-identified origin of motor hand fibers and localization of the motor cortex of the hand by functional magnetic resonance imaging (fMRI). METHODS: Preoperative fMRI during hand motor tasks was performed on 36 hemispheres in 26 patients with gliomas in or near eloquent areas. Reformatted volume-rendered surface images were labeled with the DAT's hand motor fibers and fMRI data. Five reviewers assessed the data for concordance. RESULTS: Available fMRI data were diagnostically usable in 92% (33/36 analyzed hemispheres), with DAT anatomic accuracy in the remaining cases. The DAT prediction and fMRI findings were concordant in all 9 normal hemispheres and in 20 (83%) of 24 glioma-bearing hemispheres. The 4 discordant cases resulted from substantial mass effect by large frontal tumors. CONCLUSIONS: This study validated DAT's anatomic atlas and alignment process for the expected position of the motor cortex of the hand.

Phase 1-2 study of docetaxel plus aflibercept in patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer.

BACKGROUND: Biologically targeted therapies have been postulated as a viable strategy to improve outcomes for women with ovarian cancer. We assessed the safety, tolerance, pharmacokinetics, relevant circulating and image-derived biomarkers, and clinical activity of combination aflibercept and docetaxel in this population. METHODS: For the phase 1 (pharmacokinetic) study, eligible patients had measurable, recurrent or persistent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma with a maximum of two prior chemotherapy regimens. Aflibercept was administered intravenously over three dose levels (2, 4, or 6 mg/kg; one dose every 21 days) to identify the maximum tolerated dose for the phase 2 study. Pharmacokinetics were assessed and dynamic imaging was done during a lead-in phase with single-agent aflibercept (cycle 0) and during combination therapy with intravenous docetaxel (75 mg/m(2)). Eligibility for the phase 2 study was the same as for phase 1. Patients were enrolled in a two-stage design and given aflibercept 6 mg/kg intravenously and docetaxel 75 mg/m(2) intravenously, every 3 weeks. The primary endpoint was objective response rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors version 1.0. The trial has completed enrolment and all patients are now off study. The trial is registered at ClinicalTrials.gov, number NCT00436501. FINDINGS: From the phase 1 study, the recommended phase 2 doses of aflibercept and docetaxel were found to be 6 mg/kg and 75 mg/m(2), respectively. Log-linear pharmacokinetics (for unbound aflibercept) were observed for the three dose levels. No dose-limiting toxicities were noted. 46 evaluable patients were enrolled in the phase 2 trial; 33 were platinum resistant (15 refractory) and 13 were platinum sensitive. The confirmed ORR was 54% (25 of 46; 11 patients had a complete response and 14 had a partial response). Grade 3-4 toxicities observed in more than two patients (5%) were: neutropenia in 37 patients (80%); leucopenia in 25 patients (54%); fatigue in 23 patients (50%); dyspnoea in ten patients (22%); and stomatitis in three patients (7%). Adverse events specifically associated with aflibercept were grade 1-2 hypertension in five patients (11%), and grade 2 proteinuria in one patient (2%). INTERPRETATION: Combination aflibercept plus docetaxel can be safely administered at the dose and schedule reported here, and is associated with substantial antitumour activity. These findings suggest that further clinical development of this combination in ovarian cancer is warranted. FUNDING: US National Cancer Institute, US Department of Defense, Sanofi-Aventis, Gynecologic Cancer Foundation, Marcus Foundation, and the Commonwealth Foundation.

Do brain responses to emotional images and cigarette cues differ? An fMRI study in smokers.

Chronic smoking is thought to cause changes in brain reward systems that result in overvaluation of cigarette-related stimuli and undervaluation of natural rewards. We tested the hypotheses that, in smokers, brain circuits involved in emotional processing: (i) would be more active during exposure to cigarette-related than neutral pictures; and (ii) would be less active to pleasant compared with cigarette-related pictures, suggesting a devaluation of intrinsically pleasant stimuli. We obtained whole-brain blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging data from 35 smokers during the presentation of pleasant (erotica and romance), unpleasant (mutilations and sad), neutral, and cigarette-related pictures. Whole-brain analyses showed significantly larger BOLD responses during presentation of cigarette-related pictures relative to neutral ones within the secondary visual areas, the cingulate gyrus, the frontal gyrus, the dorsal striatum, and the left insula. BOLD responses to erotic pictures exceeded responses to cigarette-related pictures in all clusters except the insula. Within the left insula we observed larger BOLD responses to cigarette-related pictures than to all other picture categories. By including intrinsically pleasant and unpleasant pictures in addition to neutral ones, we were able to conclude that the presentation of cigarette-related pictures activates brain areas supporting emotional processes, but we did not find evidence of overall reduced activation of the brain reward systems in the presence of intrinsically pleasant stimuli.

Quantitative imaging test approval and biomarker qualification: interrelated but distinct activities.

UNLABELLED: Quantitative imaging biomarkers could speed the development of new treatments for unmet medical needs and improve routine clinical care. However, it is not clear how the various regulatory and nonregulatory (eg, reimbursement) processes (often referred to as pathways) relate, nor is it clear which data need to be collected to support these different pathways most efficiently, given the time- and cost-intensive nature of doing so. The purpose of this article is to describe current thinking regarding these pathways emerging from diverse stakeholders interested and active in the definition, validation, and qualification of quantitative imaging biomarkers and to propose processes to facilitate the development and use of quantitative imaging biomarkers. A flexible framework is described that may be adapted for each imaging application, providing mechanisms that can be used to develop, assess, and evaluate relevant biomarkers. From this framework, processes can be mapped that would be applicable to both imaging product development and to quantitative imaging biomarker development aimed at increasing the effectiveness and availability of quantitative imaging. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100800/-/DC1.

MRI features of inflammatory breast cancer.

OBJECTIVE: The aim of this study was to evaluate the features of inflammatory breast carcinoma (IBC) on MRI compared with mammography and ultrasound and to better define the role of MRI in patients with this aggressive disease. MATERIALS AND METHODS: A retrospective analysis was performed of patients with newly diagnosed IBC evaluated at a single institution between 2003 and 2008. Baseline MRI examinations were performed on a 1.5- or 3-T scanner using contrast-enhanced 3D T1-weighted gradient-echo sequences with parallel imaging. MRI findings were rated in accordance with the BI-RADS MRI lexicon established by the American College of Radiology. All patients underwent concomitant mammography and ultrasound examinations. RESULTS: Eighty women with a clinical diagnosis of IBC were included in the study (median age, 52 years; age range, 25-78 years). MRI detected a primary breast lesion in 78 of 80 symptomatic breasts (98%) compared with 53 of 78 (68%) with mammography (p < 0.0001) and 75 of 80 (94%) with ultrasound. Of the 78 breasts with a primary lesion, the most common MRI finding was a mass or multiple masses (57/78, 73%). Masses were frequently multiple, small, and confluent (47/57, 82%); mass margins, irregular (43/57, 75%); and internal enhancement pattern, heterogeneous (47/57, 82%). Kinetic analysis revealed a delayed washout pattern in 66 of 78 tumors (85%). MRI showed skin thickening in 74 of 80 breasts (93%), whereas mammography showed skin thickening in 56 of 78 breasts (72%). CONCLUSION: Multiple small, confluent, heterogeneously enhancing masses and global skin thickening are key MRI features of IBC that contribute to improved detection of a primary breast cancer and delineation of disease extent compared with mammography.

Findings of the AAPM Ad Hoc committee on magnetic resonance imaging in radiation therapy: Unmet needs, opportunities, and recommendations.

The past decade has seen the increasing integration of magnetic resonance (MR) imaging into radiation therapy (RT). This growth can be contributed to multiple factors, including hardware and software advances that have allowed the acquisition of high-resolution volumetric data of RT patients in their treatment position (also known as MR simulation) and the development of methods to image and quantify tissue function and response to therapy. More recently, the advent of MR-guided radiation therapy (MRgRT) - achieved through the integration of MR imaging systems and linear accelerators - has further accelerated this trend. As MR imaging in RT techniques and technologies, such as MRgRT, gain regulatory approval worldwide, these systems will begin to propagate beyond tertiary care academic medical centers and into more community-based health systems and hospitals, creating new opportunities to provide advanced treatment options to a broader patient population. Accompanying these opportunities are unique challenges related to their adaptation, adoption, and use including modification of hardware and software to meet the unique and distinct demands of MR imaging in RT, the need for standardization of imaging techniques and protocols, education of the broader RT community (particularly in regards to MR safety) as well as the need to continue and support research, and development in this space. In response to this, an ad hoc committee of the American Association of Physicists in Medicine (AAPM) was formed to identify the unmet needs, roadblocks, and opportunities within this space. The purpose of this document is to report on the major findings and recommendations identified. Importantly, the provided recommendations represent the consensus opinions of the committee's membership, which were submitted in the committee's report to the AAPM Board of Directors. In addition, AAPM ad hoc committee reports differ from AAPM task group reports in that ad hoc committee reports are neither reviewed nor ultimately approved by the committee's parent groups, including at the council and executive committee level. Thus, the recommendations given in this summary should not be construed as being endorsed by or official recommendations from the AAPM.

Multi-site, multi-platform comparison of MRI T1 measurement using the system phantom.

Recent innovations in quantitative magnetic resonance imaging (MRI) measurement methods have led to improvements in accuracy, repeatability, and acquisition speed, and have prompted renewed interest to reevaluate the medical value of quantitative T1. The purpose of this study was to determine the bias and reproducibility of T1 measurements in a variety of MRI systems with an eye toward assessing the feasibility of applying diagnostic threshold T1 measurement across multiple clinical sites. We used the International Society of Magnetic Resonance in Medicine/National Institute of Standards and Technology (ISMRM/NIST) system phantom to assess variations of T1 measurements, using a slow, reference standard inversion recovery sequence and a rapid, commonly-available variable flip angle sequence, across MRI systems at 1.5 tesla (T) (two vendors, with number of MRI systems n = 9) and 3 T (three vendors, n = 18). We compared the T1 measurements from inversion recovery and variable flip angle scans to ISMRM/NIST phantom reference values using Analysis of Variance (ANOVA) to test for statistical differences between T1 measurements grouped according to MRI scanner manufacturers and/or static field strengths. The inversion recovery method had minor over- and under-estimations compared to the NMR-measured T1 values at both 1.5 T and 3 T. Variable flip angle measurements had substantially greater deviations from the NMR-measured T1 values than the inversion recovery measurements. At 3 T, the measured variable flip angle T1 for one vendor is significantly different than the other two vendors for most of the samples throughout the clinically relevant range of T1. There was no consistent pattern of discrepancy between vendors. We suggest establishing rigorous quality control procedures for validating quantitative MRI methods to promote confidence and stability in associated measurement techniques and to enable translation of diagnostic threshold from the research center to the entire clinical community.

Reproducibility of perfusion parameters in dynamic contrast-enhanced MRI of lung and liver tumors: effect on estimates of patient sample size in clinical trials and on individual patient responses.

OBJECTIVE: Dynamic contrast-enhanced MRI (DCE-MRI) is a potentially useful noninvasive technique for assessing tissue perfusion, particularly in the context of solid tumors and targeted antiangiogenic and antivascular therapies. Our aim was to determine the reproducibility of perfusion parameters derived at DCE-MRI of tumors of the lung and liver, the most common sites of metastasis. SUBJECTS AND METHODS: Patients with lung and liver tumors underwent two sequential DCE-MRI examinations 2-7 days apart without any intervening therapy. The volume transfer constant between blood plasma and the extravascular extracellular space (K(trans)) and blood-normalized initial area under the signal intensity-time curve (initial AUC(BN)) were computed with a two-compartment pharmacokinetic model. Differences in parameters were assessed with within-patient coefficients of variation. RESULTS: Twenty-three patients had evaluable tumors (12 lung, 11 liver). The within-patient coefficients of variation for K(trans) and initial AUC(BN) for liver lesions were 8.9% and 9.9% and for lung lesions were 17.9% and 18.2%. Sample sizes for reductions in these parameters from 10% to 50% were estimated to range from two to 102 subjects. Estimates of confidence that changes observed in a given patient were due to intervening therapy rather than variability of the technique were calculated to range from 71% to 87% if a 20% reduction in a parameter was observed. CONCLUSION: The rate of reproducibility of DCE-MRI parameters is in the range of 10%-20% and is influenced by lesion location, parameters being significantly more reproducible in the liver than in the lung. These findings provide the foundation for interpretation of results and design of clinical trials in which DCE-MRI studies are used to assess objective responses.

Development of prototype shielded cervical intracavitary brachytherapy applicators compatible with CT and MR imaging.

PURPOSE: Intracavitary brachytherapy (ICBT) is an integral part of the treatment regimen for cervical cancer and, generally, outcome in terms of local disease control and complications is a function of dose to the disease bed and critical structures, respectively. Therefore, it is paramount to accurately determine the dose given via ICBT to the tumor bed as well as critical structures. This is greatly facilitated through the use of advanced three-dimensional imaging modalities, such as CT and MR, to delineate critical and target structures with an ICBT applicator inserted in vivo. These methods are not possible when using a shielded applicator due to the image artifacts generated by interovoid shielding. The authors present two prototype shielded ICBT applicators that can be utilized for artifact-free CT image acquisition. They also investigate the MR amenability and dosimetry of a novel tungsten-alloy shielding material to extend the functionality of these devices. METHODS: To accomplish artifact-free CT image acquisition, a "step-and-shoot" (S&S) methodology was utilized, which exploits the prototype applicators movable interovoid shielding. Both prototypes were placed in imaging phantoms that positioned the applicators in clinically applicable orientations. CT image sets were acquired of the prototype applicators as well as a shielded Fletcher-Williamson (sFW) ovoid. Artifacts present in each CT image set were qualitatively compared for each prototype applicator following the S&S methodology and the sFW. To test the novel tungsten-alloy shielding material's MR amenability, they constructed a phantom applicator that mimics the basic components of an ICBT ovoid. This phantom applicator positions the MR-compatible shields in orientations equivalent to the sFW bladder and rectal shields. MR images were acquired within a gadopentetate dimeglumine-doped water tank using standard pulse sequences and examined for artifacts. In addition, Monte Carlo simulations were performed to match the attenuation due to the thickness of this new shield type with current, clinically utilized ovoid shields and a 192Ir HDR/PDR source. RESULTS: Artifact-free CT images could be acquired of both generation applicators in a clinically applicable geometry using the S&S method. MR images were acquired of the phantom applicator containing shields, which contained minimal, clinically relevant artifacts. The thickness required to match the dosimetry of the MR-compatible and sFW rectal shields was determined using Monte Carlo simulations. CONCLUSIONS: Utilizing a S&S imaging method in conjunction with prototype applicators that feature movable interovoid shields, they were able to acquire artifact-free CT image sets in a clinically applicable geometry. MR images were acquired of a phantom applicator that contained shields composed of a novel tungsten alloy. Artifacts were largely limited to regions within the ovoid cap and are of no clinical interest. The second generation A3 utilizes this material for interovoid shielding.

Development and evaluation of an arterial spin-labeling digital reference object for quality control and comparison of data analysis applications.

Longitudinal assessment of quantitative imaging biomarkers (QIBs) requires a comprehensive quality control (QC) program to minimize bias and variance in measurement results. In addition, the availability of data analysis software from multiple vendors emphasizes the need for a means of quantitatively comparing the computed QIB measures produced by the applications. The purpose of this work is to describe a digital reference object (DRO) that has been developed for the evaluation of arterial spin-labeling (ASL) measurement results. The ASL DRO is a synthetic data set consisting of 10 × 10 voxel square blocks with a range of ASL control image signal-to-noise ratio (SNRControl), blood flow (BF), and proton density (PD) image SNR values (SNRControl:1-100, BF:10-210 ml/100 g min-1, SNRPD:10-100). A pseudo-continuous ASL sequence was simulated with acquisition parameters and modeled signal intensities defined according to those typically associated with clinically-acquired ASL images. ASL parameters were estimated using the commercially-available nordicICE software package (NordicNeuroLab, Inc, Milwaukee, WI). Percent bias measures and Bland-Altman analyses demonstrated decreased bias and variance with increasing SNRControl and BF values. Excellent agreement with reference values was seen for all BF values above an SNRControl of 5 (concordance correlation coefficient greater than 0.92 for all SNRPD values). The ASL DRO developed in this work allows for the evaluation of software bias and variance across physiologically-meaningful BF and SNRControl values. Such studies are essential to the transition of quantitative ASL-based BF measurements into widespread clinical research applications, and ultimately, routine clinical care.