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  • 1
    Online Resource
    Online Resource
    Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures
    Springer Science and Business Media LLC ; 2023
    In:  Nature Communications Vol. 14, No. 1 ( 2023-09-28)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2023-09-28)
    Abstract: Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate abundant private mutations or enrichment in immune cell signatures. These NE phenotypes are non-invasively identified through normalized K2 imaging signatures, which discern cell size heterogeneity on dynamic susceptibility contrast (DSC)-MRI. NE tumor populations predicted to display increased cellular proliferation by mean diffusivity (MD) MRI metrics are uniquely associated with EGFR amplification and CDKN2A homozygous deletion. The biophysical mapping of infiltrative HGG potentially enables the clinical recognition of tumor subpopulations with aggressive molecular signatures driving tumor progression, thereby informing precision medicine targeting.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-023-41559-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2553671-0
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  • 2
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    Radiogenomics to characterize regional genetic heterogeneity in glioblastoma
    Oxford University Press (OUP) ; 2017
    In:  Neuro-Oncology Vol. 19, No. 1 ( 2017-01-01), p. 128-137
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 19, No. 1 ( 2017-01-01), p. 128-137
    Abstract: Glioblastoma (GBM) exhibits profound intratumoral genetic heterogeneity. Each tumor comprises multiple genetically distinct clonal populations with different therapeutic sensitivities. This has implications for targeted therapy and genetically informed paradigms. Contrast-enhanced (CE)-MRI and conventional sampling techniques have failed to resolve this heterogeneity, particularly for nonenhancing tumor populations. This study explores the feasibility of using multiparametric MRI and texture analysis to characterize regional genetic heterogeneity throughout MRI-enhancing and nonenhancing tumor segments. Methods We collected multiple image-guided biopsies from primary GBM patients throughout regions of enhancement (ENH) and nonenhancing parenchyma (so called brain-around-tumor, [BAT]). For each biopsy, we analyzed DNA copy number variants for core GBM driver genes reported by The Cancer Genome Atlas. We co-registered biopsy locations with MRI and texture maps to correlate regional genetic status with spatially matched imaging measurements. We also built multivariate predictive decision-tree models for each GBM driver gene and validated accuracies using leave-one-out-cross-validation (LOOCV). Results We collected 48 biopsies (13 tumors) and identified significant imaging correlations (univariate analysis) for 6 driver genes: EGFR, PDGFRA, PTEN, CDKN2A, RB1, and TP53. Predictive model accuracies (on LOOCV) varied by driver gene of interest. Highest accuracies were observed for PDGFRA (77.1%), EGFR (75%), CDKN2A (87.5%), and RB1 (87.5%), while lowest accuracy was observed in TP53 (37.5%). Models for 4 driver genes (EGFR, RB1, CDKN2A, and PTEN) showed higher accuracy in BAT samples (n = 16) compared with those from ENH segments (n = 32). Conclusion MRI and texture analysis can help characterize regional genetic heterogeneity, which offers potential diagnostic value under the paradigm of individualized oncology.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/now135
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2017
    detail.hit.zdb_id: 2094060-9
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  • 3
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    Characterizing the Influence of Preload Dosing on Percent Signal Recovery (PSR) and Cerebral Blood Volume (CBV) Measurements in a Patient Population with High-Grade Glioma Using Dynamic Susceptibility Contrast MRI
    MDPI AG ; 2017
    In:  Tomography Vol. 3, No. 2 ( 2017-06-01), p. 89-95
    Details
    In: Tomography, MDPI AG, Vol. 3, No. 2 ( 2017-06-01), p. 89-95
    Abstract: With DSC-MRI, contrast agent leakage effects in brain tumors can either be leveraged for percent signal recovery (PSR) measurements or be adequately resolved for accurate relative cerebral blood volume (rCBV) measurements. Leakage effects can be dimished by administration of a preload dose before imaging and/or specific postprocessing steps. This study compares the consistency of both PSR and rCBV measurements as a function of varying preload doses in a retrospective analysis of 14 subjects with high-grade gliomas. The scans consisted of 6 DSC-MRI scans during 6 sequential bolus injections (0.05 mmol/kg). Mean PSR was calculated for tumor and normal-appearing white matter regions of interest. DSC-MRI data were corrected for leakage effects before computing mean tumor rCBV. Statistical differences were seen across varying preloads for tumor PSR (P value = 4.57E-24). Tumor rCBV values did not exhibit statistically significant differences across preloads (P value = .14) and were found to be highly consistent for clinically relevant preloads (intraclass correlation coefficient = 0.93). For a 0.05 mmol/kg injection bolus and pulse sequence parameters used, the highest PSR contrast between normal-appearing white matter and tumor occurs when no preload is used. This suggests that studies using PSR as a biomarker should acquire DSC-MRI data without preload. The finding that leakage-corrected rCBV values do not depend on the presence or dose of preload contradicts that of previous studies with dissimilar acquisition protocols. This further confirms the sensitivity of rCBV to preload dosing schemes and pulse sequence parameters and highlights the importance of standardization efforts for achieving multisite rCBV consistency.
    Type of Medium: Online Resource
    ISSN: 2379-139X
    URL: Article
    DOI: 10.18383/j.tom.2017.00004
    Language: English
    Publisher: MDPI AG
    Publication Date: 2017
    detail.hit.zdb_id: 2857000-5
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  • 4
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    Mapping murine diabetic kidney disease using chemical exchange saturation transfer MRI
    Wiley ; 2016
    In:  Magnetic Resonance in Medicine Vol. 76, No. 5 ( 2016-11), p. 1531-1541
    Details
    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
    URL: Article
    DOI: 10.1002/mrm.v76.5
    DOI: 10.1002/mrm.26045
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 1493786-4
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  • 5
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    Evaluation of single bolus, dual-echo dynamic susceptibility contrast MRI protocols in brain tumor patients
    SAGE Publications ; 2021
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 41, No. 12 ( 2021-12), p. 3378-3390
    Details
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 41, No. 12 ( 2021-12), p. 3378-3390
    Abstract: Relative cerebral blood volume (rCBV) obtained from dynamic susceptibility contrast (DSC) MRI is adversely impacted by contrast agent leakage in brain tumors. Using simulations, we previously demonstrated that multi-echo DSC-MRI protocols provide improvements in contrast agent dosing, pulse sequence flexibility, and rCBV accuracy. The purpose of this study is to assess the in-vivo performance of dual-echo acquisitions in patients with brain tumors (n = 59). To verify pulse sequence flexibility, four single-dose dual-echo acquisitions were tested with variations in contrast agent dose, flip angle, and repetition time, and the resulting dual-echo rCBV was compared to standard single-echo rCBV obtained with preload (double-dose). Dual-echo rCBV was comparable to standard double-dose single-echo protocols (mean (standard deviation) tumor rCBV 2.17 (1.28) vs. 2.06 (1.20), respectively). High rCBV similarity was observed (CCC = 0.96), which was maintained across both flip angle (CCC = 0.98) and repetition time (CCC = 0.96) permutations, demonstrating that dual-echo acquisitions provide flexibility in acquisition parameters. Furthermore, a single dual-echo acquisition was shown to enable quantification of both perfusion and permeability metrics. In conclusion, single-dose dual-echo acquisitions provide similar rCBV to standard double-dose single-echo acquisitions, suggesting contrast agent dose can be reduced while providing significant pulse sequence flexibility and complementary tumor perfusion and permeability metrics.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1177/0271678X211039597
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
    detail.hit.zdb_id: 2039456-1
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  • 6
    Online Resource
    Online Resource
    Advanced MRI Protocols to Discriminate Glioma From Treatment Effects: State of the Art and Future Directions
    Frontiers Media SA ; 2022
    In:  Frontiers in Radiology Vol. 2 ( 2022-4-15)
    Details
    In: Frontiers in Radiology, Frontiers Media SA, Vol. 2 ( 2022-4-15)
    Abstract: In the follow-up treatment of high-grade gliomas (HGGs), differentiating true tumor progression from treatment-related effects, such as pseudoprogression and radiation necrosis, presents an ongoing clinical challenge. Conventional MRI with and without intravenous contrast serves as the clinical benchmark for the posttreatment surveillance imaging of HGG. However, many advanced imaging techniques have shown promise in helping better delineate the findings in indeterminate scenarios, as posttreatment effects can often mimic true tumor progression on conventional imaging. These challenges are further confounded by the histologic admixture that can commonly occur between tumor growth and treatment-related effects within the posttreatment bed. This review discusses the current practices in the surveillance imaging of HGG and the role of advanced imaging techniques, including perfusion MRI and metabolic MRI.
    Type of Medium: Online Resource
    ISSN: 2673-8740
    URL: Article
    DOI: 10.3389/fradi.2022.809373
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 3106354-8
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  • 7
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    Tracking glioblastoma progression after initial resection with minimal reaction-diffusion models
    American Institute of Mathematical Sciences (AIMS) ; 2022
    In:  Mathematical Biosciences and Engineering Vol. 19, No. 6 ( 2022), p. 5446-5481
    Details
    In: Mathematical Biosciences and Engineering, American Institute of Mathematical Sciences (AIMS), Vol. 19, No. 6 ( 2022), p. 5446-5481
    Abstract: 〈abstract〉〈p〉We describe a preliminary effort to model the growth and progression of glioblastoma multiforme, an aggressive form of primary brain cancer, in patients undergoing treatment for recurrence of tumor following initial surgery and chemoradiation. Two reaction-diffusion models are used: the Fisher-Kolmogorov equation and a 2-population model, developed by the authors, that divides the tumor into actively proliferating and quiescent (or necrotic) cells. The models are simulated on 3-dimensional brain geometries derived from magnetic resonance imaging (MRI) scans provided by the Barrow Neurological Institute. The study consists of 17 clinical time intervals across 10 patients that have been followed in detail, each of whom shows significant progression of tumor over a period of 1 to 3 months on sequential follow up scans. A Taguchi sampling design is implemented to estimate the variability of the predicted tumors to using $ 144 $ different choices of model parameters. In $ 9 $ cases, model parameters can be identified such that the simulated tumor, using both models, contains at least 40 percent of the volume of the observed tumor. We discuss some potential improvements that can be made to the parameterizations of the models and their initialization.〈/p〉〈/abstract〉
    Type of Medium: Online Resource
    ISSN: 1551-0018
    URL: Article
    DOI: 10.3934/mbe.2022256
    Language: Unknown
    Publisher: American Institute of Mathematical Sciences (AIMS)
    Publication Date: 2022
    detail.hit.zdb_id: 2265126-3
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  • 8
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    Assessment of renal fibrosis in murine diabetic nephropathy using quantitative magnetization transfer MRI
    Wiley ; 2018
    In:  Magnetic Resonance in Medicine Vol. 80, No. 6 ( 2018-12), p. 2655-2669
    Details
    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
    URL: Article
    DOI: 10.1002/mrm.v80.6
    DOI: 10.1002/mrm.27231
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 1493786-4
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  • 9
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    Repeatability and sensitivity of high resolution blood volume mapping in mouse kidney disease
    Wiley ; 2014
    In:  Journal of Magnetic Resonance Imaging Vol. 39, No. 4 ( 2014-04), p. 866-871
    Details
    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
    URL: Article
    DOI: 10.1002/jmri.v39.4
    DOI: 10.1002/jmri.24242
    Language: English
    Publisher: Wiley
    Publication Date: 2014
    detail.hit.zdb_id: 1497154-9
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  • 10
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    Noninvasive Detection of Matrix Metalloproteinase Activity In Vivo using a Novel Magnetic Resonance Imaging Contrast Agent with a Solubility Switch
    SAGE Publications ; 2007
    In:  Molecular Imaging Vol. 6, No. 6 ( 2007-11), p. 7290.2007.00035-
    Details
    In: Molecular Imaging, SAGE Publications, Vol. 6, No. 6 ( 2007-11), p. 7290.2007.00035-
    Type of Medium: Online Resource
    ISSN: 1536-0121 , 1536-0121
    URL: Article
    DOI: 10.2310/7290.2007.00035
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2007
    detail.hit.zdb_id: 2069848-3
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