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Native T1 Mapping as an In Vivo Biomarker for the Identification of Higher-Grade Renal Cell Carcinoma

Correlation With Histopathological Findings

Adams, Lisa C., MD*; Ralla, Bernhard, MD; Jurmeister, Philipp, MD; Bressem, Keno K., MD*; Fahlenkamp, Ute L., MD*; Hamm, Bernd, MD*; Busch, Jonas, MD, PhD; Makowski, Marcus R., MD, PhD*

doi: 10.1097/RLI.0000000000000515
Original Articles

Objectives The aims of this study were to identify higher-grade clear cell renal cell carcinoma (cRCC) with native T1 mapping and to histologically correlate the results with the collagen volume fraction.

Materials and Methods For this institutional review board–approved, single-center prospective study, 68 consecutive patients received abdominal magnetic resonance imaging scans at 1.5 T between January 2017 and July 2018, using a Modified Look-Locker Inversion Recovery (MOLLI) sequence. Thirty patients with cRCC (20 men; mean age, 61.9 ± 13.1 years) who underwent partial or radical nephrectomy and histological grading according to the International Society of Urological Pathology (ISUP) classification and a separate healthy cohort of 30 individuals without renal malignancies or complex cysts (16 men; mean age, 59.7 ± 14.6 years) met the eligibility criteria. T1 values were quantitatively measured with region of interest measurements in T1 maps. Quantification of the collagen volume fraction was performed on histological sections (picrosirius red staining).

Results Native T1 values were significantly lower for lower-grade cRCC (ISUP 1 and 2) compared with higher-grade cRCC (ISUP 3 and 4; P < 0.001). A cutoff value of 1101 milliseconds distinguished higher-grade from lower-grade tumors with a sensitivity of 100% (95% confidence interval [CI], 0.69–1.00), a specificity of 85% (95% CI, 0.62–0.97), and an accuracy of 90% (95% CI, 0.73–0.98). Native T1 values were significantly associated with the histological collagen volume fraction (P < 0.05). Furthermore, T1 times in the renal cortex, medulla, and tumor tissue showed an excellent interobserver agreement.

Conclusions Native T1 mapping could represent an in vivo biomarker for the differentiation of lower- and higher-grade cRCCs, providing incremental diagnostic value beyond qualitative magnetic resonance imaging features.

Departments of *Radiology,

Urology, and

Pathology, Charité–Universitatsmedizin Berlin, Berlin, Germany.

Received for publication July 9, 2018; and accepted for publication, after revision, August 22, 2018.

Funding: M.R.M. has received grants from the Deutsche Forschungsgesellschaft (5943/31/41, SFB 1340) and German Israel Research Foundation. B.H. has received research grants for the Department of Radiology, Charité–Universitätsmedizin Berlin from the following companies: Abbott, Actelion Pharmaceuticals, Bayer Schering Pharma, Bayer Vital, BRACCO Group, Bristol-Myers Squibb, Charite Research Organisation GmbH, Deutsche Krebshilfe, Dt. Stiftung für Herzforschung, Essex Pharma, EU Programmes, Fibrex Medical Inc, Focused Ultrasound Surgery Foundation, Fraunhofer Gesellschaft, Guerbet, INC Research, lnSightec Ud, IPSEN Pharma, Kendlel MorphoSys AG, Lilly GmbH, Lundbeck GmbH, MeVis Medical Solutions AG, Nexus Oncology, Novartis, Parexel Clinical Research Organisation Service, Perceptive, Pfizer GmbH, Philipps, Sanofis-Aventis SA, Siemens, Spectranetics GmbH, Terumo Medical Corporation, TNS Healthcare GMbH, Toshiba, UCB Pharma, Wyeth Pharma, Zukunftsfond Berlin (TSB), Amgen, AO Foundation, BARD, BBraun, Boehring Ingelheimer, Brainsgate, PPD (Clinical Research Organisation), CELLACT Pharma, Celgene, CeloNova BioSciences, Covance, DC Deviees, Ine USA, Ganymed, Gilead Sciences, GlaxoSmithKline, ICON (Clinical Research Organisation), Jansen, LUX Bioseienees, MedPass, Merek, Mologen, Nuvisan, Pluristem, Quintiles, Roehe, Sehumaeher GmbH (Sponsoring eines Workshops), Seattle Geneties, Symphogen, TauRx Therapeuties Ud, Accovion, AIO (Arbeitsgemeinschaft Internistische Onkologie), ASR Advanced Sleep Research, Astellas, Theradex, Galena Biopharma, Chiltern, PRAint, lnspiremd, Medronic, Respicardia, Silena Therapeutics, Spectrum Pharmaceuticals, St Jude, TEVA, Theorem, Abbvie, Aesculap, Biotronik, Inventivhealth, ISA Therapeutics, LYSARC, MSD, Novocure, Ockham Oncology, Premier-Research, Psi-cro, Tetec-ag, Winicker-Norimed, Achaogen Inc, ADIR, AstraZenaca AB, Demira Inc, Euroscreen SA, Galmed Research and Development Ltd, GETNE, Guidant Europe NV, Holaira Inc, Immunomedics Inc, Innate Pharma, Isis Pharmaceuticals Inc, Kantar Health GmbH, MedImmune Inc, Medpace Germany GmbH (CRO), Merrimack Pharmaceuticals Inc, Millenium Pharmaceuticals Inc, Orion Corporation Orion Pharma, Pharmacyclics Inc, PIQUR Therapeutics Ltd, Pulmonx International Sárl, Servier (CRO), SGS Life Science Services (CRO), and Treshold Pharmaceuticals Inc. L.C.A. and B.R. are participants in the BIH Charité–Junior Clinician Scientist Program funded by the Charité–Universitaetsmedizin Berlin and the Berlin Institute of Health. J.B. is a participant in the BIH–Twinning Grant Program funded by the Charité–Universitaetsmedizin Berlin and the Berlin Institute of Health. The funding had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The remaining authors declare that they have no conflicts of interest and did not receive any funds. There are no patents, products in development, or marketed products to declare.

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Correspondence to: Lisa C. Adams, MD, Department of Radiology, Charité–Universitatsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. E-mail:

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