title: Histogram Analysis of CT Perfusion of Hepatocellular Carcinoma for Predicting Response to Transarterial Radioembolization: Value of Tumor Heterogeneity Assessment.
abstract: OBJECTIVE
  To evaluate in patients with hepatocellular carcinoma (HCC), whether assessment of tumor heterogeneity by histogram analysis of computed tomography (CT) perfusion helps predicting response to transarterial radioembolization (TARE).
  
  
  METHODS
  Sixteen patients (15 male; mean age 65 years; age range 47-80 years) with HCC underwent CT liver perfusion for treatment planning prior to TARE with Yttrium-90 microspheres. Arterial perfusion (AP) derived from CT perfusion was measured in the entire tumor volume, and heterogeneity was analyzed voxel-wise by histogram analysis. Response to TARE was evaluated on follow-up imaging (median follow-up, 129 days) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results of histogram analysis and mean AP values of the tumor were compared between responders and non-responders. Receiver operating characteristics were calculated to determine the parameters' ability to discriminate responders from non-responders.
  
  
  RESULTS
  According to mRECIST, 8 patients (50%) were responders and 8 (50%) non-responders. Comparing responders and non-responders, the 50th and 75th percentile of AP derived from histogram analysis was significantly different [AP 43.8/54.3 vs. 27.6/34.3 mL min(-1) 100 mL(-1)); p < 0.05], while the mean AP of HCCs (43.5 vs. 27.9 mL min(-1) 100 mL(-1); p > 0.05) was not. Further heterogeneity parameters from histogram analysis (skewness, coefficient of variation, and 25th percentile) did not differ between responders and non-responders (p > 0.05). If the cut-off for the 75th percentile was set to an AP of 37.5 mL min(-1) 100 mL(-1), therapy response could be predicted with a sensitivity of 88% (7/8) and specificity of 75% (6/8).
  
  
  CONCLUSIONS
  Voxel-wise histogram analysis of pretreatment CT perfusion indicating tumor heterogeneity of HCC improves the pretreatment prediction of response to TARE.
authors.affiliation: Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland. caecilia.reiner@usz.ch.
authors.forename: Caecilia S
authors.initials: CS
authors.lastname: Reiner
authors.affiliation: Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.
authors.forename: Sonja
authors.initials: S
authors.lastname: Gordic
authors.affiliation: Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Puippe
authors.affiliation: Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Morsbach
authors.affiliation: Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.
authors.forename: Moritz
authors.initials: M
authors.lastname: Wurnig
authors.affiliation: Division of Nuclear Medicine, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.|Clinic for Oncology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.
authors.forename: Niklaus
authors.initials: N
authors.lastname: Schaefer
authors.affiliation: Division of Nuclear Medicine, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Veit-Haibach
authors.affiliation: Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pfammatter
authors.affiliation: Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.
authors.forename: Hatem
authors.initials: H
authors.lastname: Alkadhi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D003627:Data Interpretation, Statistical; D005260:Female; D006801:Humans; D008099:Liver / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000473:pathology; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy*; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D011300:Preoperative Care; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
chemical_list: D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes
keywords: Computed tomography perfusion; Hepatocellular carcinoma; Histogram analysis; Transarterial radioembolization; Treatment response