MRI as Primary End Point for Pharmacologic Experiments of Liver Regeneration in a Murine Model of Partial Hepatectomy.
The study aimed to validate magnetic resonance imaging (MRI)-based liver volumetry as a quantitative measure of hepatic regeneration in mice subjected to partial hepatectomy, in view of routine in vivo pharmacologic studies characterizing compounds aiming to accelerate liver regeneration.



Partial hepatectomy was performed in male B6 mice (n = 47). Images were acquired in 14.5 minutes from anesthetized and spontaneously respiring animals, without any gating and without administration of contrast material. Some of the mice (n = 6) were treated with 1, 4-bis [2-(3, 5-dichloropyridyloxy)] benzene (TCPOBOP), a synthetic agonist of mouse constitutive androstane receptor, or with the corresponding vehicle (n = 6). Postmortem analyses included total liver weight and histologic Ki67 expression.



A highly significant correlation (R = 0.98, P = 1.5 × 10-14) was obtained between the MRI-derived liver volumes and the postmortem liver weights in hepatectomized, untreated mice. MRI reliably monitored enhanced murine liver regrowth following treatment with TCPOBOP, as confirmed by comparative hepatocyte proliferation (Ki67 expression) and liver weight analysis (R = 0.96, P = 2 × 10-6).



MRI-based monitoring of liver regrowth in mice without the requirement of euthanizing animals at several time points has been established. In comparison to terminal procedures, the number of hepatectomized mice needed to derive a liver (re)growth curve was reduced by a factor of 6. The feasibility of using this imaging approach in pharmacologic studies in the context of liver regeneration has been demonstrated.
Developmental and Molecular Pathways Department, Novartis Institutes for BioMedical Research, Basel, Switzerland.
Vanessa
V
Orsini
Neurosciences Department, Novartis Institutes for BioMedical Research, Basel, Switzerland.
Stefan
S
Zurbruegg
Developmental and Molecular Pathways Department, Novartis Institutes for BioMedical Research, Basel, Switzerland.
Monika
M
Pikiolek
Developmental and Molecular Pathways Department, Novartis Institutes for BioMedical Research, Basel, Switzerland.
Jan S
JS
Tchorz
Musculoskeletal Diseases Department, Novartis Institutes for BioMedical Research, Forum 1, Novartis Campus, Fabrikstr. 28.3.07, CH-4056 Basel, Switzerland. Electronic address: nicolau.beckmann@novartis.com.
Nicolau
N
Beckmann
D000818:Animals; D049109:Cell Proliferation; D000090702:Constitutive Androstane Receptor; D003287:Contrast Media; D004195:Disease Models, Animal; D006498:Hepatectomy / Q000379:methods*; D022781:Hepatocytes / Q000502:physiology; D008099:Liver / Q000000981:diagnostic imaging* / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D009929:Organ Size; D011725:Pyridines / Q000008:administration & dosage; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists
D000090702:Constitutive Androstane Receptor; D003287:Contrast Media; D011725:Pyridines; D018160:Receptors, Cytoplasmic and Nuclear; C028474:1,4-bis(2-(3,5-dichloropyridyloxy))benzene
Hepatectomy; TCPOBOP; liver; magnetic resonance imaging (MRI); partial hepatectomy; regeneration