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Mapping Hypoxia in Renal Carcinoma with Oxygen-enhanced MRI: Comparison with Intrinsic Susceptibility MRI and Pathology.

ABSTRACT: Purpose To cross-validate T1-weighted oxygen-enhanced (OE) MRI measurements of tumor hypoxia with intrinsic susceptibility MRI measurements and to demonstrate the feasibility of translation of the technique for patients. Materials and Methods Preclinical studies in nine 786-0-R renal cell carcinoma (RCC) xenografts and prospective clinical studies in eight patients with RCC were performed. Longitudinal relaxation rate changes (?R1) after 100% oxygen inhalation were quantified, reflecting the paramagnetic effect on tissue protons because of the presence of molecular oxygen. Native transverse relaxation rate (R2*) and oxygen-induced R2* change (?R2*) were measured, reflecting presence of deoxygenated hemoglobin molecules. Median and voxel-wise values of ?R1 were compared with values of R2* and ?R2*. Tumor regions with dynamic contrast agent-enhanced MRI perfusion, refractory to signal change at OE MRI (referred to as perfused Oxy-R), were distinguished from perfused oxygen-enhancing (perfused Oxy-E) and nonperfused regions. R2* and ?R2* values in each tumor subregion were compared by using one-way analysis of variance. Results Tumor-wise and voxel-wise ?R1 and ?R2* comparisons did not show correlative relationships. In xenografts, parcellation analysis revealed that perfused Oxy-R regions had faster native R2* (102.4 sec^-1 vs 81.7 sec^-1) and greater negative ?R2* (-22.9 sec^-1 vs -5.4 sec^-1), compared with perfused Oxy-E and nonperfused subregions (all P < .001), respectively. Similar findings were present in human tumors (P < .001). Further, perfused Oxy-R helped identify tumor hypoxia, measured at pathologic analysis, in both xenografts (P = .002) and human tumors (P = .003). Conclusion Intrinsic susceptibility biomarkers provide cross validation of the OE MRI biomarker perfused Oxy-R. Consistent relationship to pathologic analyses was found in xenografts and human tumors, demonstrating biomarker translation. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

SUBMITTER: Little RA

PROVIDER: S-EPMC6122194 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Mapping Hypoxia in Renal Carcinoma with Oxygen-enhanced MRI: Comparison with Intrinsic Susceptibility MRI and Pathology.

Little Ross A RA Jamin Yann Y Boult Jessica K R JKR Naish Josephine H JH Watson Yvonne Y Cheung Susan S Holliday Katherine F KF Lu Huiqi H McHugh Damien J DJ Irlam Joely J West Catharine M L CML Betts Guy N GN Ashton Garry G Reynolds Andrew R AR Maddineni Satish S Clarke Noel W NW Parker Geoff J M GJM Waterton John C JC Robinson Simon P SP O'Connor James P B JPB

Radiology 20180605 3

Purpose To cross-validate T1-weighted oxygen-enhanced (OE) MRI measurements of tumor hypoxia with intrinsic susceptibility MRI measurements and to demonstrate the feasibility of translation of the technique for patients. Materials and Methods Preclinical studies in nine 786-0-R renal cell carcinoma (RCC) xenografts and prospective clinical studies in eight patients with RCC were performed. Longitudinal relaxation rate changes (∆R1) after 100% oxygen inhalation were quantified, reflecting the par ...[more]

PMID: 29869970

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Project description:Two magnetic resonance specific ventilation imaging (SVI) techniques, namely, oxygen-enhanced proton (OE-1H) and hyperpolarized 3He (HP-3He), were compared in eight healthy supine subjects [age 32 (6) yr]. An in-house radio frequency coil array for 1H configured with the 3He transmit-receive coil in situ enabled acquisition of SVI data from two nuclei from the same slice without repositioning the subjects. After 3?×?3 voxel downsampling to account for spatial registration errors between the two SV images, the voxel-by-voxel correlation coefficient of two SV maps ranged from 0.11 to 0.63 [0.46 mean (0.17 SD); P < 0.05]. Several indexes were analyzed and compared from the tidal volume-matched SV maps: the mean of SV log-normal distribution (SVmean), the standard deviation of the distribution as a measure of SV heterogeneity (SVwidth), and the gravitational gradient (SVslope). There were no significant differences in SVmean [OE-1H: 0.28 (0.08) and HP-3He: 0.32 (0.14)], SVwidths [OE-1H: 0.28 (0.08) and HP-3He: 0.27 (0.10)], and SVslopes [OE-1H: -0.016 (0.006) cm-1 and HP-3He: -0.013 (0.007) cm-1]. Despite the statistical similarities of the population averages, Bland-Altman analysis demonstrated large individual intertechnique variability. SDs of differences in these indexes were 42% (SVmean), 46% (SVwidths), and 62% (SVslopes) of their corresponding overall mean values. The present study showed that two independent, spatially coregistered, SVI techniques presented a moderate positive voxel-by-voxel correlation. Population averages of SVmean, SVwidth, and SVslope were in close agreement. However, the lack of agreement when the data sets were analyzed individually might indicate some fundamental mechanistic differences between the techniques. NEW & NOTEWORTHY To the best of our knowledge, this is the first cross-comparison of two different specific ventilation (SV) MRI techniques in the human lung (i.e., oxygen-enhanced proton and hyperpolarized 3He). The present study showed that two types of spatially coregistered SV images presented a modest positive correlation. The two techniques also yielded similar population averages of SV indexes such as log-normal mean, SV heterogeneity, and the gravitational slope, albeit with some intersubject variability.

Project description:BACKGROUND:Cerebral blood volume (CBV) mapping with a dynamic susceptibility contrast (DSC) perfusion technique has become a clinical tool in diagnosing and follow-up of brain tumors. Ferumoxytol, a long-circulating iron oxide nanoparticle, has been tested for CBV mapping, but the optimal dose has not been established. PURPOSE:To compare ferumoxytol DSC of two different doses to standard of care gadoteridol by analyzing time-intensity curves and CBV maps in normal-appearing brain regions. STUDY TYPE:Retrospective. SUBJECTS:Fifty-four patients with various brain disorders. FIELD STRENGTH/SEQUENCE:3T MRI. DSC-MRI was performed with 0.1 mmol/kg gadoteridol and 1 day later with ferumoxytol in doses of 1 or 2 mg/kg. ASSESSMENT:Signal changes during first pass, relative CBV (rCBV) in normal-appearing thalamus, putamen, and globus pallidus, and contrast-to-noise ratio (CNR) of the CBV maps were compared between gadoteridol and various doses of ferumoxytol using an automated method. To subjectively assess the quality of the CBV maps, two blinded readers also assessed visual conspicuity of the putamen. STATISTICAL TESTS:Linear mixed effect model was used for statistical comparison. RESULTS:Compared to gadoteridol, 1 mg/kg ferumoxytol showed no difference in CNR (P = 0.6505), peak ?R2*, and rCBV in the putamen (P = 0.2669, 0.0871) or in the thalamus (P = 0.517, 0.9787); 2 mg/kg ferumoxytol increased peak ?R2* as well as the CNR (P < 0.0001), but also mildly increased rCBV in putamen and globus pallidus (P = 0.0005, 0.0012). Signal intensities during first pass remained highly above the noise level, with overlapping of 95% confidence intervals with noise only in 3 out of 162 tested regions. Compared to gadoteridol, the visual image quality showed mild improvement with 1 mg/kg (P = 0.02) and marked improvement with 2 mg/kg ferumoxytol (P < 0.0001). DATA CONCLUSION:1 mg/kg ferumoxytol provides similar imaging results to standard gadoteridol for DSC-MRI, and 2 mg/kg has a benefit of increased CNR, but may also result in mildly increased rCBV values. LEVEL OF EVIDENCE:3 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2018;48:441-448.

Dataset Information

Mapping Hypoxia in Renal Carcinoma with Oxygen-enhanced MRI: Comparison with Intrinsic Susceptibility MRI and Pathology.

Publications

Mapping Hypoxia in Renal Carcinoma with Oxygen-enhanced MRI: Comparison with Intrinsic Susceptibility MRI and Pathology.

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