The QIBA Profile for Diffusion-Weighted MRI: Apparent Diffusion Coefficient as a Quantitative Imaging Biomarker.

The apparent diffusion coefficient (ADC) provides a quantitative measure of water mobility that can be used to probe alterations in tissue microstructure due to disease or treatment. Establishment of the accepted level of variance in ADC measurements for each clinical application is critical for its successful implementation. The Diffusion-Weighted Imaging Biomarker Committee of the Quantitative Imaging Biomarkers Alliance (QIBA) has recently advanced the ADC Profile from the consensus to clinically feasible stage for the brain, liver, prostate, and breast. This profile distills multiple studies on ADC repeatability and describes detailed procedures to achieve stated performance claims on an observed ADC change within acceptable confidence limits. In addition to reviewing the current ADC Profile claims, this report has used recent literature to develop proposed updates for establishing metrology benchmarks for mean lesion ADC change that account for measurement variance. Specifically, changes in mean ADC exceeding 8% for brain lesions, 27% for liver lesions, 27% for prostate lesions, and 15% for breast lesions are claimed to represent true changes with 95% confidence. This report also discusses the development of the ADC Profile, highlighting its various stages, and describes the workflow essential to achieving a standardized implementation of advanced quantitative diffusion-weighted MRI in the clinic. The presented QIBA ADC Profile guidelines should enable successful clinical application of ADC as a quantitative imaging biomarker and ensure reproducible ADC measurements that can be used to confidently evaluate longitudinal changes and treatment response for individual patients.

Quantitative Prostate MRI, From the AJR Special Series on Quantitative Imaging.

Prostate MRI has traditionally relied on qualitative interpretation. However, quantitative components hold the potential to markedly improve performance. The ADC from DWI is probably the most widely recognized quantitative MRI biomarker and has shown strong discriminatory value for clinically significant prostate cancer (csPCa) as well as for recurrent cancer after treatment. Advanced diffusion techniques, including intravoxel incoherent motion, diffusion kurtosis, diffusion tensor imaging, and specific implementations such as restriction spectrum imaging, purport even better discrimination, but are more technically challenging. The inherent T1 and T2 of tissue also provide diagnostic value, with more advanced techniques deriving luminal water imaging and hybrid-multidimensional MRI. Dynamic contrast-enhanced imaging, primarily using a modified Tofts model, also shows independent discriminatory value. Finally, quantitative size and shape features can be combined with the aforementioned techniques and be further refined using radiomics, texture analysis, and artificial intelligence. Which technique will ultimately find widespread clinical use will depend on validation across a myriad of platforms use-cases.

Breast Multiparametric MRI for Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer: The BMMR2 Challenge.

Purpose To describe the design, conduct, and results of the Breast Multiparametric MRI for prediction of neoadjuvant chemotherapy Response (BMMR2) challenge. Materials and Methods The BMMR2 computational challenge opened on May 28, 2021, and closed on December 21, 2021. The goal of the challenge was to identify image-based markers derived from multiparametric breast MRI, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI, along with clinical data for predicting pathologic complete response (pCR) following neoadjuvant treatment. Data included 573 breast MRI studies from 191 women (mean age [±SD], 48.9 years ± 10.56) in the I-SPY 2/American College of Radiology Imaging Network (ACRIN) 6698 trial (ClinicalTrials.gov: NCT01042379). The challenge cohort was split into training (60%) and test (40%) sets, with teams blinded to test set pCR outcomes. Prediction performance was evaluated by area under the receiver operating characteristic curve (AUC) and compared with the benchmark established from the ACRIN 6698 primary analysis. Results Eight teams submitted final predictions. Entries from three teams had point estimators of AUC that were higher than the benchmark performance (AUC, 0.782 [95% CI: 0.670, 0.893], with AUCs of 0.803 [95% CI: 0.702, 0.904], 0.838 [95% CI: 0.748, 0.928], and 0.840 [95% CI: 0.748, 0.932]). A variety of approaches were used, ranging from extraction of individual features to deep learning and artificial intelligence methods, incorporating DCE and DWI alone or in combination. Conclusion The BMMR2 challenge identified several models with high predictive performance, which may further expand the value of multiparametric breast MRI as an early marker of treatment response. Clinical trial registration no. NCT01042379 Keywords: MRI, Breast, Tumor Response Supplemental material is available for this article. © RSNA, 2024.

Prospective evaluation of in vivo and phantom repeatability and reproducibility of diffusion-weighted MRI sequences on 1.5 T MRI-linear accelerator (MR-Linac) and MR simulator devices for head and neck cancers.

INTRODUCTION: Diffusion-weighted imaging (DWI) on MRI-linear accelerator (MR-linac) systems can potentially be used for monitoring treatment response and adaptive radiotherapy in head and neck cancers (HNC) but requires extensive validation. We performed technical validation to compare six total DWI sequences on an MR-linac and MR simulator (MR sim) in patients, volunteers, and phantoms. METHODS: Ten human papillomavirus-positive oropharyngeal cancer patients and ten healthy volunteers underwent DWI on a 1.5 T MR-linac with three DWI sequences: echo planar imaging (EPI), split acquisition of fast spin echo signals (SPLICE), and turbo spin echo (TSE). Volunteers were also imaged on a 1.5 T MR sim with three sequences: EPI, BLADE (vendor tradename), and readout segmentation of long variable echo trains (RESOLVE). Participants underwent two scan sessions per device and two repeats of each sequence per session. Repeatability and reproducibility within-subject coefficient of variation (wCV) of mean ADC were calculated for tumors and lymph nodes (patients) and parotid glands (volunteers). ADC bias, repeatability/reproducibility metrics, SNR, and geometric distortion were quantified using a phantom. RESULTS: In vivo repeatability/reproducibility wCV for parotids were 5.41%/6.72%, 3.83%/8.80%, 5.66%/10.03%, 3.44%/5.70%, 5.04%/5.66%, 4.23%/7.36% for EPIMR-linac, SPLICE, TSE, EPIMR sim, BLADE, RESOLVE. Repeatability/reproducibility wCV for EPIMR-linac, SPLICE, TSE were 9.64%/10.28%, 7.84%/8.96%, 7.60%/11.68% for tumors and 7.80%/9.95%, 7.23%/8.48%, 10.82%/10.44% for nodes. All sequences except TSE had phantom ADC biases within ± 0.1x10-3 mm2/s for most vials (EPIMR-linac, SPLICE, and BLADE had 2, 3, and 1 vials out of 13 with larger biases, respectively). SNR of b = 0 images was 87.3, 180.5, 161.3, 171.0, 171.9, 130.2 for EPIMR-linac, SPLICE, TSE, EPIMR sim, BLADE, RESOLVE. CONCLUSION: MR-linac DWI sequences demonstrated near-comparable performance to MR sim sequences and warrant further clinical validation for treatment response assessment in HNC.

Test-retest repeatability of ADC in prostate using the multi b-Value VERDICT acquisition.

PURPOSE: VERDICT (Vascular, Extracellular, Restricted Diffusion for Cytometry in Tumours) MRI is a multi b-value, variable diffusion time DWI sequence that allows generation of ADC maps from different b-value and diffusion time combinations. The aim was to assess precision of prostate ADC measurements from varying b-value combinations using VERDICT and determine which protocol provides the most repeatable ADC. MATERIALS AND METHODS: Forty-one men (median age: 67.7 years) from a prior prospective VERDICT study (April 2016-October 2017) were analysed retrospectively. Men who were suspected of prostate cancer and scanned twice using VERDICT were included. ADC maps were formed using 5b-value combinations and the within-subject standard deviations (wSD) were calculated per ADC map. Three anatomical locations were analysed per subject: normal TZ (transition zone), normal PZ (peripheral zone), and index lesions. Repeated measures ANOVAs showed which b-value range had the lowest wSD, Spearman correlation and generalized linear model regression analysis determined whether wSD was related to ADC magnitude and ROI size. RESULTS: The mean lesion ADC for b0b1500 had the lowest wSD in most zones (0.18-0.58x10-4 mm2/s). The wSD was unaffected by ADC magnitude (Lesion: p = 0.064, TZ: p = 0.368, PZ: p = 0.072) and lesion Likert score (p = 0.95). wSD showed a decrease with ROI size pooled over zones (p = 0.019, adjusted regression coefficient = -1.6x10-3, larger ROIs for TZ versus PZ versus lesions). ADC maps formed with a maximum b-value of 500 s/mm2 had the largest wSDs (1.90-10.24x10-4 mm2/s). CONCLUSION: ADC maps generated from b0b1500 have better repeatability in normal TZ, normal PZ, and index lesions.

Conformance of a 3T radiotherapy MRI scanner to the QIBA Diffusion Profile.

PURPOSE: To assess the technical performance of the apparent diffusion coefficient (ADC) on a dedicated 3T radiotherapy scanner, using a standardized phantom and sequences. Investigations into factors that could impact the technical performance of ADC in the clinic were also completed, including changing the slice-encoded imaging direction and the reference sample ADC value. METHODS: ADC acquisitions were performed monthly on an isotropic diffusion phantom over 1 year. Measurements of ADC %bias, coefficients of variation for short-/long-term repeatability and precision (CVST /CVLT and CVP ), and b-value dependency (Depb ) were calculated. The measurements were then assessed according to the Quantitative Imaging Biomarker Alliance (QIBA) Diffusion Profile specifications. RESULTS: The average of all measurements over the year was within Profile recommended ranges. This included when testing was performed in different imaging directions, and on samples that had different ADC reference values (0.4-1.1 µm2 /ms). Results in the axial plane for the central water vial included a bias of +0.05%, CVST /CVLT /CVP  = 0.1%/ 0.9%/0.4% and Depb  = 0.4%. CONCLUSIONS: The technical performance of ADC on a radiotherapy dedicated MRI scanner over the course of 12 months was considered conformant to the QIBA Profile. Quantifying these metrics and factors that may affect the performance is essential in progressing the use of ADC clinically: ensuring that the observed change of ADC in a tissue is due to a physiological response and not measurement variability.

Impact of Alternate b-Value Combinations and Metrics on the Predictive Performance and Repeatability of Diffusion-Weighted MRI in Breast Cancer Treatment: Results from the ECOG-ACRIN A6698 Trial.

In diffusion-weighted MRI (DW-MRI), choice of b-value influences apparent diffusion coefficient (ADC) values by probing different aspects of the tissue microenvironment. As a secondary analysis of the multicenter ECOG-ACRIN A6698 trial, the purpose of this study was to investigate the impact of alternate b-value combinations on the performance and repeatability of tumor ADC as a predictive marker of breast cancer treatment response. The final analysis included 210 women who underwent standardized 4-b-value DW-MRI (b = 0/100/600/800 s/mm2) at multiple timepoints during neoadjuvant chemotherapy treatment and a subset (n = 71) who underwent test−retest scans. Centralized tumor ADC and perfusion fraction (fp) measures were performed using variable b-value combinations. Prediction of pathologic complete response (pCR) based on the mid-treatment/12-week percent change in each metric was estimated by area under the receiver operating characteristic curve (AUC). Repeatability was estimated by within-subject coefficient of variation (wCV). Results show that two-b-value ADC calculations provided non-inferior predictive value to four-b-value ADC calculations overall (AUCs = 0.60−0.61 versus AUC = 0.60) and for HR+/HER2− cancers where ADC was most predictive (AUCs = 0.75−0.78 versus AUC = 0.76), p < 0.05. Using two b-values (0/600 or 0/800 s/mm2) did not reduce ADC repeatability over the four-b-value calculation (wCVs = 4.9−5.2% versus 5.4%). The alternate metrics ADCfast (b ≤ 100 s/mm2), ADCslow (b ≥ 100 s/mm2), and fp did not improve predictive performance (AUCs = 0.54−0.60, p = 0.08−0.81), and ADCfast and fp demonstrated the lowest repeatability (wCVs = 6.71% and 12.4%, respectively). In conclusion, breast tumor ADC calculated using a simple two-b-value approach can provide comparable predictive value and repeatability to full four-b-value measurements as a marker of treatment response.

Repeatability and Reproducibility Assessment of the Apparent Diffusion Coefficient in the Prostate: A Trial of the ECOG-ACRIN Research Group (ACRIN 6701).

BACKGROUND: Uncertainty regarding the reproducibility of the apparent diffusion coefficient (ADC) hampers the use of quantitative diffusion-weighted imaging (DWI) in evaluation of the prostate with magnetic resonance imaging MRI. The quantitative imaging biomarkers alliance (QIBA) profile for quantitative DWI claims a within-subject coefficient of variation (wCV) for prostate lesion ADC of 0.17. Improved understanding of ADC reproducibility would aid the use of quantitative diffusion in prostate MRI evaluation. PURPOSE: Evaluation of the repeatability (same-day) and reproducibility (multi-day) of whole-prostate and focal-lesion ADC assessment in a multi-site setting. STUDY TYPE: Prospective multi-institutional. SUBJECTS: Twenty-nine males, ages 53 to 80 (median 63) years, following diagnosis of prostate cancer, 10 with focal lesions. FIELD STRENGTH/SEQUENCE: 3T, single-shot spin-echo diffusion-weighted echo-planar sequence with four b-values. ASSESSMENT: Sites qualified for the study using an ice-water phantom with known ADC. Readers performed DWI analyses at visit 1 ("V1") and visit 2 ("V2," 2-14 days after V1), where V2 comprised scans before ("V2pre") and after ("V2post") a "coffee-break" interval with subject removal and repositioning. A single reader segmented the whole prostate. Two readers separately placed region-of-interests for focal lesions. STATISTICAL TESTS: Reproducibility and repeatability coefficients for whole prostate and focal lesions derived from median pixel ADC. We estimated the wCV and 95% confidence interval using a variance stabilizing transformation and assessed interreader reliability of focal lesion ADC using the intraclass correlation coefficient (ICC). RESULTS: The ADC biases from b0 -b600 and b0 -b800 phantom scans averaged 1.32% and 1.44%, respectively; mean b-value dependence was 0.188%. Repeatability and reproducibility of whole prostate median pixel ADC both yielded wCVs of 0.033 (N = 29). In 10 subjects with an evaluable focal lesion, the individual reader wCVs were 0.148 and 0.074 (repeatability) and 0.137 and 0.078 (reproducibility). All time points demonstrated good to excellent interreader reliability for focal lesion ADC (ICCV1  = 0.89; ICCV2pre  = 0.76; ICCV2post  = 0.94). DATA CONCLUSION: This study met the QIBA claim for prostate ADC. Test-retest repeatability and multi-day reproducibility were largely equivalent. Interreader reliability for focal lesion ADC was high across time points. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2 TOC CATEGORY: Pelvis.

Development, validation, qualification, and dissemination of quantitative MR methods: Overview and recommendations by the ISMRM quantitative MR study group.

On behalf of the International Society for Magnetic Resonance in Medicine (ISMRM) Quantitative MR Study Group, this article provides an overview of considerations for the development, validation, qualification, and dissemination of quantitative MR (qMR) methods. This process is framed in terms of two central technical performance properties, i.e., bias and precision. Although qMR is confounded by undesired effects, methods with low bias and high precision can be iteratively developed and validated. For illustration, two distinct qMR methods are discussed throughout the manuscript: quantification of liver proton-density fat fraction, and cardiac T1 . These examples demonstrate the expansion of qMR methods from research centers toward widespread clinical dissemination. The overall goal of this article is to provide trainees, researchers, and clinicians with essential guidelines for the development and validation of qMR methods, as well as an understanding of necessary steps and potential pitfalls for the dissemination of quantitative MR in research and in the clinic.

Cardiac Enhanced Recovery After Surgery: Early Outcomes in a Community Setting.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) programs have demonstrated improved outcomes in noncardiac surgery. More recently, ERAS has been applied to cardiac surgery with promising results. We have implemented cardiac ERAS at our community-based program, aiming to improve all phases of care, and now report our early results. METHODS: We retrospectively analyzed 73 consecutive patients treated with ERAS care compared with 74 patients treated before implementing ERAS. Our ERAS program consisted of 6 perioperative care bundles including enhanced patient education, shortened preoperative fasting period and oral carbohydrate load, postoperative nausea prophylaxis, multimodal opioid-sparing analgesia, early extubation, and early mobilization. RESULTS: ERAS patients required significantly less opioids captured as total morphine milligram equivalents (MME) (median 35.0 vs 75.3; P < .001), less nausea as determined by fewer total ondansetron rescue doses (median 0 vs 0.5; P = .011), and less lightheadedness (P = .028) compared with pre-ERAS patients. Postoperative mobility was significantly better (postoperative day 4: 95% vs 81%; P = .013) and postoperative length of stay was lower for ERAS care but did not reach statistical significance (median 4 days vs 5 days; P = .06). There was no difference in pain or glucose control or in early extubation. CONCLUSIONS: Cardiac ERAS significantly decreased opioid use, nausea, and lightheadedness and improved functional outcome for cardiac surgical patients in a community hospital.

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.

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.

Postoperative Multimodal Analgesia in Cardiac Surgery.

Multimodal pain management of cardiac surgical patients is a paradigm shift in postoperative care. This promising approach features complementary medications and techniques that spare opioids and improves symptomatic and functional recovery. Although the specific elements remain to be defined, the collaboration of the health care team and patient and continuous iterative programmatic improvements are important pillars of this approach.

Radiofrequency transmit calibration: A multi-center evaluation of vendor-provided radiofrequency transmit mapping methods.

PURPOSE: To determine the accuracy and test-retest repeatability of fast radiofrequency (RF) transmit measurement approaches used in Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI). Spatial variation in the transmitted RF field introduces bias and increased variance in quantitative DCE-MRI metrics including tracer kinetic parameter maps. If unaccounted for, these errors can dominate all other sources of bias and variance. The amount and pattern of variation depend on scanner-specific hardware and software. METHODS: Human tissue mimicking torso and brain phantoms were constructed. RF transmit maps were measured and compared across eight different commercial scanners, from three major vendors, and three clinical sites. Vendor-recommended rapid methods for RF mapping were compared to a slower reference method. Imaging was repeated at all sites after 2 months. Ranges and magnitude of RF inhomogeneity were compared scanner-wise at two time points. Limits of Agreement of vendor-recommended methods and double-angle reference method were assessed. RESULTS: At 3 T, B1 + inhomogeneity spans across 35% in the head and 120% in the torso. Fast vendor provided methods are within 30% agreement with the reference double angle method for both the head and the torso phantom. CONCLUSIONS: If unaccounted for, B1 + inhomogeneity can severely impact tracer-kinetic parameter estimation. Depending on the scanner, fast vendor provided B1 + mapping sequences allow unbiased and reproducible measurements of B1 + inhomogeneity to correct for this source of bias.

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

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

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.

Author Correction: Large T1 contrast enhancement using superparamagnetic nanoparticles in ultra-low field MRI.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Assessment of quantitative magnetic resonance imaging metrics in the brain through the use of a novel phantom.

OBJECTIVE: Multisite and longitudinal neuroimaging studies are important in uncovering trajectories of recovery and neurodegeneration following traumatic brain injury (TBI) and concussion through the use of diffusion tensor imaging (DTI) and other imaging modalities. This study assessed differences in anisotropic diffusion measurement across four scanners using a human and a novel phantom developed in conjunction with the Chronic Effects of Neurotrauma Consortium. METHOD: Human scans provided measurement within biological tissue, and the novel physical phantom provided measures of anisotropic intra-tubular diffusion to serve as a model for intra-axonal water diffusion. Intra- and inter-scanner measurement variances were compared, and the impact on effect size was calculated. RESULTS: Intra-scanner test-retest reliability estimates for fractional anisotropy (FA) demonstrated relative stability over testing intervals. The human tissue and phantom showed similar FA ranges, high linearity and large within-device effect sizes. However, inter-scanner measures of FA indicated substantial differences, some of which exceeded typical DTI effect sizes in mild TBI. CONCLUSION: The diffusion phantom may be used to better elucidate inter-scanner variability in DTI-based measurement and provides an opportunity to better calibrate results obtained from scanners used in multisite and longitudinal studies. Novel solutions are being evaluated to understand and potentially overcome these differences.

Large T1 contrast enhancement using superparamagnetic nanoparticles in ultra-low field MRI.

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely investigated and utilized as magnetic resonance imaging (MRI) contrast and therapy agents due to their large magnetic moments. Local field inhomogeneities caused by these high magnetic moments are used to generate T2 contrast in clinical high-field MRI, resulting in signal loss (darker contrast). Here we present strong T1 contrast enhancement (brighter contrast) from SPIONs (diameters from 11 nm to 22 nm) as observed in the ultra-low field (ULF) MRI at 0.13 mT. We have achieved a high longitudinal relaxivity for 18 nm SPION solutions, r1 = 615 s-1 mM-1, which is two orders of magnitude larger than typical commercial Gd-based T1 contrast agents operating at high fields (1.5 T and 3 T). The significantly enhanced r1 value at ultra-low fields is attributed to the coupling of proton spins with SPION magnetic fluctuations (Brownian and Néel) associated with a low frequency peak in the imaginary part of AC susceptibility (χ"). SPION-based T1-weighted ULF MRI has the advantages of enhanced signal, shorter imaging times, and iron-oxide-based nontoxic biocompatible agents. This approach shows promise to become a functional imaging technique, similar to PET, where low spatial resolution is compensated for by important functional information.

Analysis of variability of fractional anisotropy values at 3T using a novel diffusion tensor imaging phantom.

We employed a novel diffusion tensor imaging phantom to study intra- and interscanner reproducibility on two 3T magnetic resonance (MR) scanners. Using a phantom containing thousands of hollow micron-size tubes in complex arrays, we performed two experiments using a b value of 1000 s/ms2 on two Siemens 3T Trio scanners. First, we performed 12-direction scans. Second, on one scanner, we performed two 64-direction protocols with different repetition times (TRs). We used a one-way analysis of variance to calculate differences between scanners and the Mann-Whitney U test to assess differences between 12-direction and 64-direction data. We calculated the coefficient of variation (CoV) for intrascanner and interscanner data. For 12-direction protocols, mean fractional anisotropy (FA) was 0.3003 for Scanner 1 (four scans) and 0.3094 for Scanner 2 (three scans). Lowest FA value on Scanner 1 was 2.56 standard deviations below the mean of Scanner 2. For 64-direction scans, mean FA was 0.2640 for 4000 ms TR and 0.2582 for 13,200 ms TR scans. For 12-direction scans, within-scanner CoV was 0.0326 for Scanner 1 and 0.0240 for Scanner 2; between-scanner CoV was 0.032. For 64-direction scans, CoV was 0.056 for TR 4000 ms and 0.0533 for TR 13,200 ms. The difference between median FA values of 12-direction and 64-direction scans was statistically significant ( p < 0.001). We found relatively good reproducibility on any single MR scanner. FA values from one scanner were sometimes significantly below the mean FA of another scanner, which has important implications for clinical use of DTI.