{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:34:49Z","timestamp":1772325289951,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,4,17]],"date-time":"2017-04-17T00:00:00Z","timestamp":1492387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Physics"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>Conventional two\u2010compartment modeling of tissue microcirculation is used for tracer kinetic analysis of dynamic contrast\u2010enhanced (<jats:styled-content style=\"fixed-case\">DCE<\/jats:styled-content>) computed tomography or magnetic resonance imaging studies although it is well\u2010known that the underlying assumption of an instantaneous mixing of the administered contrast agent (<jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>) in capillaries is far from being realistic. It was thus the aim of the present study to provide theoretical and computational evidence in favor of a conceptually alternative modeling approach that makes it possible to characterize the bias inherent to compartment modeling and, moreover, to approximately correct for it.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Starting from a two\u2010region distributed\u2010parameter model that accounts for spatial gradients in <jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content> concentrations within blood\u2010tissue exchange units, a modified lumped two\u2010compartment exchange model was derived. It has the same analytical structure as the conventional two\u2010compartment model, but indicates that the apparent blood flow identifiable from measured <jats:styled-content style=\"fixed-case\">DCE<\/jats:styled-content> data is substantially overestimated, whereas the three other model parameters (i.e., the permeability\u2010surface area product as well as the volume fractions of the plasma and interstitial distribution space) are unbiased. Furthermore, a simple formula was derived to approximately compute a bias\u2010corrected flow from the estimates of the apparent flow and permeability\u2010surface area product obtained by model fitting. To evaluate the accuracy of the proposed modeling and bias correction method, representative noise\u2010free <jats:styled-content style=\"fixed-case\">DCE<\/jats:styled-content> curves were analyzed. They were simulated for 36 microcirculation and four input scenarios by an axially distributed reference model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>As analytically proven, the considered two\u2010compartment exchange model is structurally identifiable from tissue residue data. The apparent flow values estimated for the 144 simulated tissue\/input scenarios were considerably biased. After bias\u2010correction, the deviations between estimated and actual parameter values were (11.2\u00a0\u00b1\u00a06.4) % (vs. (105\u00a0\u00b1\u00a021) % without correction) for the flow, (3.6\u00a0\u00b1\u00a06.1) % for the permeability\u2010surface area product, (5.8\u00a0\u00b1\u00a04.9) % for the vascular volume and (2.5\u00a0\u00b1\u00a04.1) % for the interstitial volume; with individual deviations of more than 20% being the exception and just marginal. Increasing the duration of <jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content> administration only had a statistically significant but opposite effect on the accuracy of the estimated flow (declined) and intravascular volume (improved).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Physiologically well\u2010defined tissue parameters are structurally identifiable and accurately estimable from <jats:styled-content style=\"fixed-case\">DCE<\/jats:styled-content> data by the conceptually modified two\u2010compartment model in combination with the bias correction. The accuracy of the bias\u2010corrected flow is nearly comparable to that of the three other (theoretically unbiased) model parameters. As compared to conventional two\u2010compartment\u00a0modeling, this feature constitutes a major advantage for tracer kinetic analysis of both preclinical and clinical <jats:styled-content style=\"fixed-case\">DCE<\/jats:styled-content> imaging studies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mp.12196","type":"journal-article","created":{"date-parts":[[2017,3,8]],"date-time":"2017-03-08T21:36:49Z","timestamp":1489009009000},"page":"1809-1822","source":"Crossref","is-referenced-by-count":8,"title":["Two\u2010compartment modeling of tissue microcirculation revisited"],"prefix":"10.1002","volume":"44","author":[{"given":"Gunnar","family":"Brix","sequence":"first","affiliation":[{"name":"Department of Medical Radiation Protection Federal Office for Radiation Protection Ingolst\u00e4dter Landstra\u00dfe 1 D\u201085764 Oberschleissheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona","family":"Salehi Ravesh","sequence":"additional","affiliation":[{"name":"Department of Congenital Heart Disease and Pediatric Cardiology University Hospital Schleswig\u2010Holstein Arnold\u2010Heller\u2010Stra\u00dfe 3 D\u201024105 Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Griebel","sequence":"additional","affiliation":[{"name":"Department of Medical Radiation Protection Federal Office for Radiation Protection Ingolst\u00e4dter Landstra\u00dfe 1 D\u201085764 Oberschleissheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,4,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13244-011-0125-0"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2014.11.011"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910160111"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910170208"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004728-199107000-00018"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1259\/0007-1285-64-761-409"},{"key":"e_1_2_10_8_1","first-page":"S31","article-title":"Tracerkinetic modelling of tumour angiogenesis based on dynamic contrast\u2010enhanced CT and MRI measurements","volume":"3","author":"Brix G","year":"2010","journal-title":"Eur J Nucl Med Mol Imag"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/57\/2\/R1"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1118\/1.4898202"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.210.1.r99ja46269"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1118\/1.3147145"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.20161"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2323031198"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.22005"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-009-1621-1"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.22217"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2013.08.008"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/59\/7\/1533"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3109\/0284186X.2014.937879"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.2478\/raon-2014-0030"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0136725"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.26189"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/RLI.0000000000000309"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02476432"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1987.88"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1109\/TBME.2002.807657"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1109\/TBME.2007.910682"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/10739680701410850"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02477493"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.52.1.96"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1959.197.6.1205"},{"key":"e_1_2_10_33_1","volume-title":"Tracer Kinetics in Biomedical Research","author":"Cobelli C","year":"2000"},{"key":"e_1_2_10_34_1","first-page":"549","volume-title":"Handbook of Physiology. Section\u00a02. The Cardiovascular System","author":"Bassingthwaighte JB","year":"1984"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.65.4.997"},{"key":"e_1_2_10_36_1","volume-title":"Der Mensch in Zahlen: Eine Datensammlung in Tabellen mit \u00fcber 20.000 Einzelwerten","author":"Kunsch K","year":"2000"},{"key":"e_1_2_10_37_1","first-page":"3239","article-title":"Transport of molecules in the tumor interstitium: a review","volume":"78","author":"Jain RK","year":"1987","journal-title":"Cancer Res"},{"key":"e_1_2_10_38_1","first-page":"2641","article-title":"Determinants of tumor blood flow: a review","volume":"48","author":"Jain RK","year":"1988","journal-title":"Cancer Res"},{"key":"e_1_2_10_39_1","unstructured":"International Life Sciences Institute Risk Science Institute.Physiological parameters for PBPK models 1994.https:\/\/nepis.epa.gov\/Exe\/ZyPDF.cgi\/9100K030.PDF?Dockey=9100K030.PDF. Assessed February 20 2017."},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/0470035439.ch2"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027755"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1109\/TMI.2009.2016212"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.22868"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmp.2011.03.004"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/0025-5564(70)90132-X"}],"container-title":["Medical Physics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmp.12196","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aapm.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mp.12196","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T06:23:47Z","timestamp":1696573427000},"score":1,"resource":{"primary":{"URL":"https:\/\/aapm.onlinelibrary.wiley.com\/doi\/10.1002\/mp.12196"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,17]]},"references-count":44,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,5]]}},"alternative-id":["10.1002\/mp.12196"],"URL":"https:\/\/doi.org\/10.1002\/mp.12196","archive":["Portico"],"relation":{},"ISSN":["0094-2405","2473-4209"],"issn-type":[{"value":"0094-2405","type":"print"},{"value":"2473-4209","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,17]]}}}