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  • 1
    In: Magnetic Resonance in Medicine, Wiley, Vol. 76, No. 5 ( 2016-11), p. 1531-1541
    Abstract: Diabetic nephropathy (DN) is the leading cause of renal failure; however, current clinical tests are insufficient for assessing this disease. DN is associated with changes in renal metabolites, so we evaluated the utility of chemical exchange saturation transfer (CEST) imaging to detect changes characteristic of this disease. Methods Sensitivity of CEST imaging at 7 Tesla to DN was evaluated by imaging diabetic mice [db/db, db/db endothelial nitric oxide synthase (eNOS)−/−] that show different levels of nephropathy as well as by longitudinal imaging (8 to 24 weeks). Nondiabetic (db/m) mice were used as controls. Results Compared with nondiabetic mice, the CEST contrasts of hydroxyl metabolites that correspond to glucose and glycogen were significantly increased in papilla (P), inner medulla (IM), and outer medulla (OM) in db/db and db/db eNOS−/− kidneys at 16 weeks. The db/db eNOS−/− mice that showed advanced nephropathy exhibited greater CEST effects in OM and significant CEST contrasts were also observed in cortex. Longitudinally, db/db mice exhibited progressive increases in hydroxyl signals in IM+P and OM from 12 to 24 weeks and an increase was also observed in cortex at 24 weeks. Conclusion CEST MRI can be used to measure changes of hydroxyl metabolites in kidney during progression of DN. Magn Reson Med 76:1531–1541, 2016. © 2015 International Society for Magnetic Resonance in Medicine
    Type of Medium: Online Resource
    ISSN: 0740-3194 , 1522-2594
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2016
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  • 2
    In: Magnetic Resonance in Medicine, Wiley, Vol. 80, No. 6 ( 2018-12), p. 2655-2669
    Abstract: Renal fibrosis is a hallmark of progressive renal disease; however, current clinical tests are insufficient for assessing renal fibrosis. Here we evaluated the utility of quantitative magnetization transfer MRI in detecting renal fibrosis in a murine model of progressive diabetic nephropathy (DN). Methods The db/db eNOS‐/‐ mice, a well‐recognized model of progressive DN, and normal wild‐type mice were imaged at 7T. The quantitative magnetization transfer data were collected in coronal plane using a 2D magnetization transfer prepared spoiled gradient echo sequence with a Gaussian‐shaped presaturation pulse. Parameters were derived using a two‐pool fitting model. A normal range of cortical pool size ratio (PSR) was defined as Mean±2SD of wild‐type kidneys ( N  = 20). The cortical regions whose PSR values exceeded this threshold (threshold PSR) were assessed. The correlations between the PSR‐based and histological (collagen IV or picrosirius red stain) fibrosis measurements were evaluated. Results Compared with wild‐type mice, moderate increases in mean PSR values and scattered clusters of high PSR region were observed in cortex of DN mouse kidneys. Abnormally high PSR regions (% area) that were detected by the threshold PSR were significantly increased in renal cortexes of DN mice. These regions progressively increased on aging and highly correlated with histological fibrosis measures, while the mean PSR values correlated much less. Conclusion Renal fibrosis in DN can be assessed by the quantitative magnetization transfer MRI and threshold analysis. This technique may be used as a novel imaging biomarker for DN and other renal diseases.
    Type of Medium: Online Resource
    ISSN: 0740-3194 , 1522-2594
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
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  • 3
    In: Journal of Magnetic Resonance Imaging, Wiley, Vol. 39, No. 4 ( 2014-04), p. 866-871
    Abstract: To evaluate the repeatability of MRI‐derived relative blood volume (RBV) measurements in mouse kidneys across subjects and days and to evaluate sensitivity of this approach to renal pathology. Materials and Methods A 7 Tesla MRI system and an intravascular iron‐oxide contrast agent were used to acquire spin‐echo–based renal RBV maps in 10 healthy mice on 2 consecutive days. Renal RBV maps were also acquired in the Alport and unilateral ureteral obstruction mouse models of renal disease. Results The average renal RBV measured on consecutive days was 19.97 ± 1.50 and 19.86 ± 1.62, yielding a concordance correlation coefficient of 0.94, indicating that this approach is highly repeatable. In the disease models, the RBV values were regionally dissimilar and substantially lower than those found in control mice. Conclusion In vivo renal iron‐oxide–based RBV mapping in mice complements the physiological information obtained from conventional assays of kidney function and could shed new insights into the pathological mechanisms of kidney disease. J. Magn. Reson. Imaging 2014;39:866–871. © 2013 Wiley Periodicals, Inc .
    Type of Medium: Online Resource
    ISSN: 1053-1807 , 1522-2586
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2014
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  • 4
    In: Magnetic Resonance in Medicine, Wiley, Vol. 76, No. 2 ( 2016-08), p. 635-644
    Type of Medium: Online Resource
    ISSN: 0740-3194
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2016
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  • 5
    In: Magnetic Resonance in Medicine, Wiley, Vol. 72, No. 2 ( 2014-08), p. 471-476
    Abstract: This study investigates amide proton transfer (APT) and nuclear overhauser enhancement (NOE) in phantoms and 9L tumors in rat brains at 9.4 Tesla, using a recently developed method that can isolate different contributions to exchange. Methods Chemical exchange rotation transfer (CERT) was used to quantify APT and NOEs through subtraction of signals acquired at two irradiation flip angles, but with the same average irradiation power. Results CERT separates and quantifies specific APT and NOE signals without contamination from other proton pools, and thus overcomes a key shortcoming of conventional CEST asymmetry approaches. CERT thus has increased specificity, though at the cost of decreased signal strength. In vivo experiments show that the APT effect acquired with CERT in 9L rat tumors (3.1%) is relatively greater than that in normal tissue (2.5%), which is consistent with previous CEST asymmetry analysis. The NOE effect centered at −1.6 ppm shows substantial image contrast within the tumor and between the tumor and the surrounding tissue, while the NOE effect centered at −3.5 ppm shows little contrast. Conclusion CERT provides an image contrast that is more specific to chemical exchange than conventional APT by means of asymmetric CEST Z‐spectra analysis. Magn Reson Med 72:471–476, 2014. © 2013 Wiley Periodicals, Inc.
    Type of Medium: Online Resource
    ISSN: 0740-3194 , 1522-2594
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2014
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  • 6
    In: Magnetic Resonance in Medicine, Wiley, Vol. 86, No. 6 ( 2021-12), p. 3082-3095
    Abstract: The purpose of this study was to develop a spiral‐based combined spin‐ and gradient‐echo (spiral‐SAGE) method for simultaneous dynamic contrast‐enhanced (DCE‐MRI) and dynamic susceptibility contrast MRI (DSC‐MRI). Methods Using this sequence, we obtained gradient‐echo TEs of 1.69 and 26 ms, a SE TE of 87.72 ms, with a TR of 1663 ms. Using an iterative SENSE reconstruction followed by deblurring, spiral‐induced image artifacts were minimized. Healthy volunteer images are shown to demonstrate image quality using the optimized reconstruction, as well as for comparison with EPI‐based SAGE. A bioreactor phantom was used to compare dynamic‐contrast time courses with both spiral‐SAGE and EPI‐SAGE. A proof‐of‐concept cohort of patients with brain tumors shows the range of hemodynamic maps available using spiral‐SAGE. Results Comparison of spiral‐SAGE images with conventional EPI‐SAGE images illustrates substantial reductions of image distortion and artifactual image intensity variations. Bioreactor phantom data show similar dynamic contrast time courses between standard EPI‐SAGE and spiral‐SAGE for the second and third echoes, whereas first‐echo data show improvements in quantifying T 1 changes with shorter echo times. In a cohort of patients with brain tumors, spiral‐SAGE–based perfusion and permeability maps are shown with comparison with the standard single‐echo EPI perfusion map. Conclusion Spiral‐SAGE provides a substantial improvement for the assessment of perfusion and permeability by mitigating artifacts typically encountered with EPI and by providing a shorter echo time for improved characterization of permeability. Spiral‐SAGE enables quantification of perfusion, permeability, and vessel architectural parameters, as demonstrated in brain tumors.
    Type of Medium: Online Resource
    ISSN: 0740-3194 , 1522-2594
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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  • 7
    In: Magnetic Resonance in Medicine, Wiley, Vol. 60, No. 3 ( 2008-09), p. 718-726
    Abstract: Dark lumen MRI colonography detects colonic polyps by minimization of the intestinal lumen signal intensity. Here we validate the use of perfluorinated oil as an intestinal‐filling agent for dark lumen MRI studies in mice, enabling the physiological characterization of colonic polyps by dynamic contrast‐enhanced MRI. In control and Min (multiple intestinal neoplasia) mice with and without pretreatment with oral dextran sodium sulfate (DSS), polyps as small as 0.94 mm diameter were consistently identified using standard 2D gradient echo imaging (voxel size, 0.23 × 0.16 × 0.5 mm). In serial studies, polyp growth rates were heterogeneous with an average ≈5% increase in polyp volume per day. In DSS‐treated control mice the colon wall contrast agent extravasation rate constant, K trans , and extravascular extracellular space volume fraction, v e , values were measured for the first time and found to be 0.10 ± 0.03 min −1 and 0.23 ± 0.09, respectively. In DSS‐treated Min mice, polyp K trans values (0.09 ± 0.04 min −1 ) were similar to those in the colon wall but the v e values were substantially lower (0.16 ± 0.03), suggesting increased cellular density. The functional dark‐lumen colonography approach described herein provides new opportunities for the noninvasive assessment of gastrointestinal disease pathology and treatment response in mouse models. Magn Reson Med 60:718–726, 2008. © 2008 Wiley‐Liss, Inc.
    Type of Medium: Online Resource
    ISSN: 0740-3194 , 1522-2594
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2008
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  • 8
    In: Journal of Magnetic Resonance Imaging, Wiley, Vol. 55, No. 6 ( 2022-06), p. 1745-1758
    Abstract: Diffusion‐weighted imaging (DWI) is commonly used to detect prostate cancer, and a major clinical challenge is differentiating aggressive from indolent disease. Purpose To compare 14 site‐specific parametric fitting implementations applied to the same dataset of whole‐mount pathologically validated DWI to test the hypothesis that cancer differentiation varies with different fitting algorithms. Study Type Prospective. Population Thirty‐three patients prospectively imaged prior to prostatectomy. Field Strength/Sequence 3 T, field‐of‐view optimized and constrained undistorted single‐shot DWI sequence. Assessment Datasets, including a noise‐free digital reference object (DRO), were distributed to the 14 teams, where locally implemented DWI parameter maps were calculated, including mono‐exponential apparent diffusion coefficient (MEADC), kurtosis (K), diffusion kurtosis (DK), bi‐exponential diffusion (BID), pseudo‐diffusion (BID*), and perfusion fraction (F). The resulting parametric maps were centrally analyzed, where differentiation of benign from cancerous tissue was compared between DWI parameters and the fitting algorithms with a receiver operating characteristic area under the curve (ROC AUC). Statistical Test Levene's test, P   〈  0.05 corrected for multiple comparisons was considered statistically significant. Results The DRO results indicated minimal discordance between sites. Comparison across sites indicated that K, DK, and MEADC had significantly higher prostate cancer detection capability (AUC range = 0.72–0.76, 0.76–0.81, and 0.76–0.80 respectively) as compared to bi‐exponential parameters (BID, BID*, F) which had lower AUC and greater between site variation (AUC range = 0.53–0.80, 0.51–0.81, and 0.52–0.80 respectively). Post‐processing parameters also affected the resulting AUC, moving from, for example, 0.75 to 0.87 for MEADC varying cluster size. Data Conclusion We found that conventional diffusion models had consistent performance at differentiating prostate cancer from benign tissue. Our results also indicated that post‐processing decisions on DWI data can affect sensitivity and specificity when applied to radiological–pathological studies in prostate cancer. Level of Evidence 1 Technical Efficacy Stage 3
    Type of Medium: Online Resource
    ISSN: 1053-1807 , 1522-2586
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 1497154-9
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  • 9
    In: Journal of Magnetic Resonance Imaging, Wiley, Vol. 51, No. 2 ( 2020-02), p. 547-553
    Abstract: Dynamic susceptibility contrast (DSC)‐MRI analysis pipelines differ across studies and sites, potentially confounding the clinical value and use of the derived biomarkers. Purpose/Hypothesis To investigate how postprocessing steps for computation of cerebral blood volume (CBV) and residue function dependent parameters (cerebral blood flow [CBF], mean transit time [MTT] , capillary transit heterogeneity [CTH]) impact glioma grading. Study Type Retrospective study from The Cancer Imaging Archive (TCIA). Population Forty‐nine subjects with low‐ and high‐grade gliomas. Field Strength/Sequence 1.5 and 3.0T clinical systems using a single‐echo echo planar imaging (EPI) acquisition. Assessment Manual regions of interest (ROIs) were provided by TCIA and automatically segmented ROIs were generated by k‐means clustering. CBV was calculated based on conventional equations. Residue function dependent biomarkers (CBF, MTT, CTH) were found by two deconvolution methods: circular discretization followed by a signal‐to‐noise ratio (SNR)‐adapted eigenvalue thresholding (Method 1) and Volterra discretization with L‐curve‐based Tikhonov regularization (Method 2). Statistical Tests Analysis of variance, receiver operating characteristics (ROC), and logistic regression tests. Results MTT alone was unable to statistically differentiate glioma grade ( P   〉  0.139). When normalized, tumor CBF, CTH, and CBV did not differ across field strengths ( P   〉  0.141). Biomarkers normalized to automatically segmented regions performed equally (rCTH AUROC is 0.73 compared with 0.74) or better (rCBF AUROC increases from 0.74–0.84; rCBV AUROC increases 0.78–0.86) than manually drawn ROIs. By updating the current deconvolution steps (Method 2), rCTH can act as a classifier for glioma grade ( P   〈  0.007), but not if processed by current conventional DSC methods (Method 1) ( P   〉  0.577). Lastly, higher‐order biomarkers (eg, rCBF and rCTH) along with rCBV increases AUROC to 0.92 for differentiating tumor grade as compared with 0.78 and 0.86 (manual and automatic reference regions, respectively) for rCBV alone. Data Conclusion With optimized analysis pipelines, higher‐order perfusion biomarkers (rCBF and rCTH) improve glioma grading as compared with CBV alone. Additionally, postprocessing steps impact thresholds needed for glioma grading. Level of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:547–553.
    Type of Medium: Online Resource
    ISSN: 1053-1807 , 1522-2586
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 10
    In: Magnetic Resonance in Medicine, Wiley, Vol. 83, No. 1 ( 2020-01), p. 109-123
    Abstract: Brain tumor dynamic susceptibility contrast (DSC) MRI is adversely impacted by T 1 and contrast agent leakage effects that result in inaccurate hemodynamic metrics. While multi‐echo acquisitions remove T 1 leakage effects, there is no consensus on the optimal set of acquisition parameters. Using a computational approach, we systematically evaluated a wide range of acquisition strategies to determine the optimal multi‐echo DSC‐MRI perfusion protocol. Methods Using a population‐based DSC‐MRI digital reference object (DRO), we assessed the influence of preload dosing (no preload and full dose preload), field strength (1.5 and 3T), pulse sequence parameters (echo time, repetition time, and flip angle), and leakage correction on relative cerebral blood volume (rCBV) and flow (rCBF) accuracy. We also compared multi‐echo DSC‐MRI protocols with standard single‐echo protocols. Results Multi‐echo DSC‐MRI is highly consistent across all protocols, and multi‐echo rCBV (with or without use of a preload dose) had higher accuracy than single‐echo rCBV. Regression analysis showed that choice of repetition time and flip angle had minimal impact on multi‐echo rCBV and rCBV, indicating the potential for significant flexibility in acquisition parameters. The echo time combination had minimal impact on rCBV, though longer echo times should be avoided, particularly at higher field strengths. Leakage correction improved rCBV accuracy in all cases. Multi‐echo rCBF was less biased than single‐echo rCBF, although rCBF accuracy was reduced overall relative to rCBV. Conclusions Multi‐echo acquisitions were more robust than single‐echo, essentially decoupling both repetition time and flip angle from rCBV accuracy. Multi‐echo acquisitions obviate the need for preload dosing, although leakage correction to remove residual leakage effects remains compulsory for high rCBV accuracy.
    Type of Medium: Online Resource
    ISSN: 0740-3194 , 1522-2594
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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