RationaleLung T1 MRI is a potential method to assess cystic fibrosis (CF) lung disease that is safe, quick, and widely available, but there are no data in children with mild CF lung disease.ObjectiveAssess the ability of lung T1 MRI to detect abnormalities in children with mild CF lung disease.MethodsWe performed T1 MRI, multiple breath washout (MBW), chest computed tomography (CT), and spirometry in a cohort of 45 children with mild CF lung disease (6-11 years of age).Main ResultsDespite mean normal ppFEV1 values, the majority of children with CF in this study exhibited mild lung disease evident in lung clearance index (LCI) measured by MBW, chest CT Brody scores, and percent normal lung perfusion (%NLP) measured by T1 MRI. The %NLP correlated with chest CT Brody scores, as did LCI, but %NLP and LCI did not correlate with each other. Analysis of the Brody subscores showed that %NLP and LCI largely correlated with different Brody subscores.ConclusionsT1 MRI can detect mild CF lung disease in children and correlates with chest CT findings. The %NLP from T1 MRI and LCI correlate with different chest CT Brody subscores, suggesting they provide complementary information about CF lung disease.

Quantitative MRI enables direct quantification of contrast agent concentrations in contrast-enhanced scans. However, the lengthy scan times required by conventional methods are inadequate for tracking contrast agent transport dynamically in mouse brain. We developed a 3D MR fingerprinting (MRF) method for simultaneous T1 and T2 mapping across the whole mouse brain with 4.3-min temporal resolution. We designed a 3D MRF sequence with variable acquisition segment lengths and magnetization preparations on a 9.4T preclinical MRI scanner. Model-based reconstruction approaches were employed to improve the accuracy and speed of MRF acquisition. The method's accuracy for T1 and T2 measurements was validated in vitro, while its repeatability of T1 and T2 measurements was evaluated in vivo (n=3). The utility of the 3D MRF sequence for dynamic tracking of intracisternally infused Gd-DTPA in the whole mouse brain was demonstrated (n=5). Phantom studies confirmed accurate T1 and T2 measurements by 3D MRF with an undersampling factor up to 48. Dynamic contrast-enhanced (DCE) MRF scans achieved a spatial resolution of 192 x 192 x 500 um3 and a temporal resolution of 4.3 min, allowing for the analysis and comparison of dynamic changes in concentration and transport kinetics of intracisternally infused Gd-DTPA across brain regions. The sequence also enabled highly repeatable, high-resolution T1 and T2 mapping of the whole mouse brain (192 x 192 x 250 um3) in 30 min. We present the first dynamic and multi-parametric approach for quantitatively tracking contrast agent transport in the mouse brain using 3D MRF.

Conventional diagnostic images from Magnetic Resonance Imaging (MRI) are typically qualitative and require subjective interpretation. Alternatively, quantitative MRI (qMRI) methods have become more prevalent in recent years with multiple clinical and preclinical imaging applications. Quantitative MRI studies on preclinical MRI scanners are being used to objectively assess tissues and pathologies in animal models and to evaluate new molecular MRI contrast agents. Low-field preclinical MRI scanners (≤3.0T) are particularly important in terms of evaluating these new MRI contrast agents at human MRI field strengths. Unfortunately, these low-field preclinical qMRI methods are challenged by long acquisition times, intrinsically low MRI signal levels, and susceptibility to motion artifacts. In this study, we present a new rapid qMRI method for a preclinical 3.0T MRI scanner that combines a Spiral Acquisition with a Matching-Based Algorithm (SAMBA) to rapidly and quantitatively evaluate MRI contrast agents. In this initial development, we compared SAMBA with gold-standard Spin Echo MRI methods using Least Squares Fitting (SELSF) in vitro phantoms and demonstrated shorter scan times without compromising measurement accuracy or repeatability. These initial results will pave the way for future in vivo qMRI studies using state-of-the-art chemical probes.

Figure 1 (A and B) Effect of DA discontinuation: (A) Between-group comparison of change in whole-lung MCC (WLAveClr90).(B) Scatter plot of baseline vs. 6-week WLAveClr90.(C and D) Effect of hypertonic saline discontinuation: (C) Betweengroup comparison of change in whole-lung MCC (WLAveClr90).(D) Scatter plot of baseline vs. 6-week WLAveClr90.Conclusions: These results suggest that PwCF on ETI with mild disease do not experience subclinical deterioration in MCC that could affect health outcomes after discontinuing hypertonic saline.Those stopping dornase alfa could benefit from better MCC after stopping this treatment.

•Better outcome measures are needed to support clinical trials in patients with CF.•Extra-pulmonary disease manifestations are becoming more important in CF.•MRI provides a radiation free imaging alternative to X-ray and CT.•MRI can provide quantitative assessments of the lungs and other organs.•MRI techniques have been developed for the heart, kidneys, pancreas, and liver.

Background Quantitative T1 and T2 mapping in the abdomen provides valuable information in tissue characterization but is technically challenging due to respiratory motions. The proposed technique integrates magnetic resonance fingerprinting (MRF) and pilot tone (PT) navigator with retrospective gating to provide simultaneous quantification of multiple tissue properties in a single acquisition without breath-holding or patient set-up. Purpose To develop a free-breathing abdominal MRF technique for quantitative mapping in the abdomen. Study Type Prospective. Population Twelve healthy volunteers. Field Strength/Sequence A 3 T, two-dimensional (2D) and three-dimensional (3D) spiral MRF sequence with fast imaging with steady-state free precession (FISP) readout. Assessment The PT navigator was compared to standard respiratory belt performance. The T1 and T2 values acquired using 2D and 3D MRF with and without PT were obtained in a phantom and compared to reference values. Digital phantom simulation was performed to evaluate PT MRF reconstruction with varying breathing patterns. In the in vivo studies, T1 and T2 values derived from PT 2D MRF were compared to 2D breath-hold MRF. T1 and T2 values derived from PT 3D MRF were compared to published values. Statistical Tests Principal component analysis (PCA), linear regression, relative error, Pearson correlation, paired Student's t-test, Bland-Altman Analysis. Results The phantom study showed PT MRF T1 values had a mean difference of 0.2% +/- 0.1%, and T2 values had a mean difference of 0.1% +/- 0.4% when compared to no-PT MRF values. The digital phantom experiment suggested the T1 and T2 maps at both end-exhalation and end-inhalation states resemble the corresponding ground-truth maps. Data conclusion The phantom study showed good agreement between MRF T1 and T2 values and with reference values. In vivo studies demonstrated that 2D and 3D quantitative imaging in the abdomen could be achieved with integration of PT navigation with MRF reconstruction using retrospective gating of respiratory motion. Evidence Level 1 Technical Efficacy Stage 1

Background MR fingerprinting (MRF) provides rapid and simultaneous quantification of multiple tissue parameters in a single scan. Purpose To evaluate a rapid kidney MRF technique at 3.0 T in phantoms, healthy volunteers, and patients. Materials and Methods A 15-second kidney MRF acquisition was designed with 12 acquisition segments, a range of low flip angles (5°-12°), multiple magnetization preparation schema (T1, T2, and fat suppression), and an undersampled spiral trajectory. This technique was first validated in vitro using standardized T1 and T2 phantoms. Kidney T1 and T2 maps were then obtained for 10 healthy adult volunteers (mean age ± standard deviation, 35 years ± 13; six men) and three pediatric patients with autosomal recessive polycystic kidney disease (ARPKD) (mean age, 10 years ± 3; two boys) between August 2019 and October 2020 to evaluate the method in vivo. Results Results in nine phantoms showed good agreement with spin-echo-based T1 and T2 values (R2 > 0.99). In vivo MRF kidney T1 and T2 assessments in healthy adult volunteers (cortex: T1, 1362 msec ± 5; T2, 64 msec ± 5; medulla: T1, 1827 msec ± 94; T2, 69 msec ± 3) were consistent with values in the literature but with improved precision in comparison with prior MRF implementations. In vivo MRF-based kidney T1 and T2 values with and without B1 correction were in good agreement (R2 > 0.96, P < .001), demonstrating limited sensitivity to B1 field inhomogeneities. Additional MRF reconstructions using the first nine segments of the MRF profiles (11-second acquisition time) were in good agreement with the reconstructions using 12 segments (15-second acquisition time) (R2 > 0.87, P < .001). Repeat kidney MRF scans for the three patients with ARPKD on successive days also demonstrated good reproducibility (T1 and T2: <3% difference). Conclusion A kidney MR fingerprinting method provided in vivo kidney T1 and T2 maps at 3.0 T in a single breath hold with improved precision and no need for B1 correction. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Laustsen in this issue.

Poor prognosis for glioblastoma (GBM) is a consequence of the aggressive and infiltrative nature of gliomas where individual cells migrate away from the main tumor to distant sites, making complete surgical resection and treatment difficult. In this manuscript, we characterize an invasive pediatric glioma model and determine if nanoparticles linked to a peptide recognizing the GBM tumor biomarker PTPmu can specifically target both the main tumor and invasive cancer cells in adult and pediatric glioma models. Using both iron and lipid-based nanoparticles, we demonstrate by magnetic resonance imaging, optical imaging, histology, and iron quantification that PTPmu-targeted nanoparticles effectively label adult gliomas. Using PTPmu-targeted nanoparticles in a newly characterized orthotopic pediatric SJ-GBM2 model, we demonstrate individual tumor cell labeling both within the solid tumor margins and at invasive and dispersive sites.

Autosomal recessive polycystic kidney disease (ARPKD) is a rare but potentially lethal genetic disorder typically characterized by diffuse renal microcysts. Clinical trials for patients with ARPKD are not currently possible due to the absence of sensitive measures of ARPKD kidney disease progression and/or therapeutic efficacy. In this study, animal and human magnetic resonance imaging (MRI) scanners were used to obtain quantitative kidney T1 and T2 relaxation time maps for both excised kidneys from bpk and wild-type (WT) mice as well as for a pediatric patient with ARPKD and a healthy adult volunteer. Mean kidney T1 and T2 relaxation times showed significant increases with age (p < 0.05) as well as significant increases in comparison to WT mice (p < 2 × 10−10). Significant or nearly significant linear correlations were observed for mean kidney T1 (p = 0.030) and T2 (p = 0.054) as a function of total kidney volume, respectively. Initial magnetic resonance fingerprinting assessments in a patient with ARPKD showed visible increases in both kidney T1 and T2 in comparison to the healthy volunteer. These preclinical and initial clinical MRI studies suggest that renal T1 and T2 relaxometry may provide an additional outcome measure to assess cystic kidney disease progression in patients with ARPKD.

Quantitative Magnetic Resonance Imaging (MRI) involves pixel-wise mapping of longitudinal relaxation time T1, transverse relaxation time T2 and proton density M0 and other relevant parameters at each location in the tissue to be characterized. The goal of this study is to investigate potential benefits of Magnetic Resonance Fingerprinting in quantifying T1 relaxation times in metastatic breast tumor using radial acquisition in tumor with high temporal and spatial resolution.

In this pilot study, we developed and optimized a spatially-constrained convolutional neural network to accelerate the scan time for 2D kidney Magnetic Resonance Fingerprinting (MRF). Our results suggest that an acceleration factor of 3 can be achieved with the proposed method, which shortens the 2D breath-hold MRF scan from 15 sec to 5 sec. In addition, the deep learning based approach can be applied for T1 and T2 quantification of both normal renal tissues and pathologies including renal cell carcinoma.

Motivation: Quantitative MR provides the opportunity of quantifying concentration of contrast agent and its transport in cerebrospinal fluid (CSF) in the whole brain. Goal(s): To develop a fast multi-parametric mapping method tailored to dynamically and quantitatively assessing Gd-DTPA transport in mouse brain. Approach: We designed and validated a new 3D MR fingerprinting (MRF) sequence with subspace-based reconstruction to simultaneously track T1 and T2 changes in mouse brain following intrathecal contrast infusion with a temporal resolution of <4.5 min at 9.4T. Results: Dynamic T1 and T2 changes allowed direct quantification of transport kinetics in different brain regions between multiple subjects without normalization. Impact: We present the first 3D MR fingerprinting method for dynamic quantification of contrast agent transport in rodent brains. With unprecedented speed, accuracy, and robustness, our method offers unlimited opportunities for multi-parametric quantification in various preclinical imaging applications.

Motivation: There are no clinically available therapies for ARPKD. Goal(s): We evaluated the ability of T1 and T2 from MR Fingerprinting (MRF) to assess kidney cystic burden and Arterial Spin Labeling (ASL) to assess kidney perfusion to detect and stage ARPKD kidney disease. Approach: 12 ARPKD patients and 10 healthy adult volunteers were scanned on a Siemens 3T with kidney MRF and ASL MRI methods to generate kidney cortical perfusion maps. Results: Significant increases in kidney T1 and T2, and reduced perfusion were observed between ARPKD patients and healthy volunteers (p<0.001) and between ARPKD patients with early and mild-to-moderate CKD based on eGFR (p<0.03). Impact: The multi-modal MRI biomarkers in combination evaluated were able to distinctly stratify all three cohorts, including the two ARPKD patient cohorts, demonstrating the utility of a multi-modal MRI approach during future clinical trials aimed at limiting ARPKD kidney disease progression.