Vessel-Selective 4D-MRA Using Superselective Pseudocontinuous Arterial Spin-Labeling with Keyhole and View-Sharing for Visualizing Intracranial Dural AVFs.

BACKGROUND AND PURPOSE: An accurate assessment of the hemodynamics of an intracranial dural AVF is necessary for treatment planning. We aimed to investigate the utility of 4D-MRA based on superselective pseudocontinuous arterial spin-labeling with CENTRA-keyhole and view-sharing (4D-S-PACK) for the vessel-selective visualization of intracranial dural AVFs. MATERIALS AND METHODS: We retrospectively analyzed the images of 21 patients (12 men and 9 women; mean age, 62.2 [SD,19.2] years) with intracranial dural AVFs, each of whom was imaged with DSA, 4D-S-PACK, and nonselective 4D-MRA based on pseudocontinuous arterial spin-labeling combined with CENTRA-keyhole and view-sharing (4D-PACK). The shunt location, venous drainage patterns, feeding artery identification, and Borden classification were evaluated by 2 observers using both MRA methods on separate occasions. Vessel selectivity was evaluated on 4D-S-PACK. RESULTS: Shunt locations were correctly evaluated in all 21 patients by both observers on both MRA methods. With 4D-S-PACK, observers 1 and 2 detected 76 (80.0%, P < .001) and 73 (76.8%, P < .001) feeding arteries of the 95 feeding arteries identified on DSA but only 39 (41.1%) and 46 (48.4%) feeding arteries with nonselective 4D-PACK, respectively. Both observers correctly identified 10 of the 11 patients with cortical venous reflux confirmed by DSA with both 4D-S-PACK and 4D-PACK (sensitivity = 90.9%, specificity = 90.9% for each method), and they made accurate Borden classifications in 20 of the 21 patients (95.2%) on both MRA methods. Of the 84 vessel territories examined, vessel selectivity was graded 3 or 4 in 73 (91.2%) and 66 (88.0%) territories by observers 1 and 2, respectively. CONCLUSIONS: 4D-S-PACK is useful for the identification of feeding arteries and accurate classifications of intracranial dural AVFs and can be a useful noninvasive clinical tool.

Analysis of effects and indications of cryosurgery for oral mucoceles.

Cryosurgery is a recognized method for the treatment of mucoceles in the oral cavity. In this study, cryosurgery was used for mucoceles at the lip or buccal mucosa, and the effect and the indication were evaluated clinically. The subjects were patients with a clinical diagnosis of mucocele on the lip or buccal mucosa and who chose cryosurgery after procedures for both surgical excision and cryosurgery for the lesion were explained. Cryosurgery was performed with a freezing device using liquid nitrogen without local anesthesia. Twenty-four patients chose cryosurgery, including seven preschool children. There were no serious adverse events during and after cryosurgery. Healing progress after cryosurgery was not affected by patient age, lesion size, or how long the patients had the lesion. Two cases later underwent surgical excision because cryosurgery was not successful. Twenty-three patients chose surgical excision, one case had a recurrence. The number of younger patients who chose cryosurgery was significantly higher than that who chose surgical excision. This study suggests that cryosurgery is effective for mucoceles of the lip or buccal mucosa and is a simple and safe treatment method, especially for preschool children.

Spiral T1 Spin-Echo for Routine Postcontrast Brain MRI Exams: A Multicenter Multireader Clinical Evaluation.

BACKGROUND AND PURPOSE: Spiral MR imaging has several advantages compared with Cartesian MR imaging that can be leveraged for added clinical value. A multicenter multireader study was designed to compare spiral with standard-of-care Cartesian postcontrast structural brain MR imaging on the basis of relative performance in 10 metrics of image quality, artifact prevalence, and diagnostic benefit. MATERIALS AND METHODS: Seven clinical sites acquired 88 total subjects. For each subject, sites acquired 2 postcontrast MR imaging scans: a spiral 2D T1 spin-echo, and 1 of 4 routine Cartesian 2D T1 spin-echo/TSE scans (fully sampled spin-echo at 3T, 1.5T, partial Fourier, TSE). The spiral acquisition matched the Cartesian scan for scan time, geometry, and contrast. Nine neuroradiologists independently reviewed each subject, with the matching pair of spiral and Cartesian scans compared side-by-side, and scored on 10 image-quality metrics (5-point Likert scale) focused on intracranial assessment. The Wilcoxon signed rank test evaluated relative performance of spiral versus Cartesian, while the Kruskal-Wallis test assessed interprotocol differences. RESULTS: Spiral was superior to Cartesian in 7 of 10 metrics (flow artifact mitigation, SNR, GM/WM contrast, image sharpness, lesion conspicuity, preference for diagnosing abnormal enhancement, and overall intracranial image quality), comparable in 1 of 10 metrics (motion artifacts), and inferior in 2 of 10 metrics (susceptibility artifacts, overall extracranial image quality) related to magnetic susceptibility (P < .05). Interprotocol comparison confirmed relatively higher SNR and GM/WM contrast for partial Fourier and TSE protocol groups, respectively (P < .05). CONCLUSIONS: Spiral 2D T1 spin-echo for routine structural brain MR imaging is feasible in the clinic with conventional scanners and was preferred by neuroradiologists for overall postcontrast intracranial evaluation.

Balanced MR cholangiopancreatography with motion-sensitised driven-equilibrium (MSDE) preparation: feasibility of Gd-EOB-DTPA-enhanced biliary examination.

AIM: To evaluate the effectiveness of motion-sensitised driven-equilibrium (MSDE)-prepared balanced magnetic resonance cholangiopancreatography (MRCP) in a gadolinium ethoxybenzyl diethylene triamine pentaacetic acid (Gd-EOB-DTPA)-enhanced study compared to conventional T2-weighted MRCP. MATERIALS AND METHODS: Fifteen patients (seven male and eight female patients) prospectively underwent conventional three-dimensional turbo spin-echo T2-weighted MRCP and MSDE-balanced MRCP using a 1.5 T MRI system after hepatobiliary phase image acquisition. For quantitative evaluation, the contrast-to-noise ratio (CNR) of the common hepatic duct to liver tissue was calculated. For qualitative analysis, two radiologists evaluated the depiction of the biliary system and main pancreatic duct (MPD) using a scoring system. Signal suppression of the portal vein (PV) and hepatic vein (HV) on MSDE-balanced MRCP was also scored. RESULTS: MSDE-balanced MRCP showed significantly higher CNR than T2-weighted MRCP. For all biliary structures, the mean depiction scores of MSDE-balanced MRCP were significantly higher than those of T2-weighted MRCP, whereas the mean depiction score of MPD with MSDE-balanced MRCP was significantly lower than that of T2-weighted MRCP. Signal suppression of the PV and HV was thought to be clinically sufficient. CONCLUSIONS: MSDE-balanced MRCP more clearly depicted biliary structures compared with T2-weighted MRCP in a Gd-EOB-DTPA-enhanced study. This sequence may be utilised for routine MRCP on Gd-EOB-DTPA-enhanced MRI.

Heterogeneity of non-cancerous liver parenchyma on gadoxetic acid-enhanced MRI: an imaging biomarker for hepatocellular carcinoma development in chronic liver disease.

AIM: To clarify whether the heterogeneity of non-cancerous liver parenchyma (NLP) in the hepatobiliary phase on gadoxetic acid enhanced magnetic resonance imaging (MRI) is correlated with hepatocellular carcinoma (HCC) development. MATERIALS AND METHODS: Institutional review board approval was obtained, and the requirements for informed consent were waived for this retrospective study. The imaging characteristics of 84 patients with chronic liver disease who underwent gadoxetic acid-enhanced 3T MRI between January 2013 and October 2014 were examined retrospectively. For the evaluation of the heterogeneity of the intensity in the hepatobiliary phase, the largest possible region of interest was placed on the NLP, and the skewness and kurtosis were calculated using ImageJ software. Skewness is the degree of asymmetry of a histogram, and kurtosis is a measure of the peak. Based on the median values of kurtosis and skewness, the patients were classified into four categories and the categories were compared between the 49 patients with HCC (HCC group) and the 35 patients without HCC (non-HCC group). RESULTS: Kurtosis was significantly higher in the HCC group compared to the non-HCC group (1.19±1.15 versus 0.43±0.83; p=0.0006). Skewness was significantly lower in the HCC group than in the non-HCC group (1.19±1.15 versus 0.43±0.83; p=0.0152). In a multivariate logistic analysis, the category showing lower-than-the-median (-0.1185) skewness and higher-than-the-median (0.547) kurtosis was significantly and independently associated with HCC development (p=0.0031). CONCLUSION: The heterogeneity of NLP in the hepatobiliary phase on gadoxetic acid enhanced MRI may reflect the development of HCC.

Wall Enhancement of the Intracranial Aneurysms Revealed by Magnetic Resonance Vessel Wall Imaging Using Three-Dimensional Turbo Spin-Echo Sequence with Motion-Sensitized Driven-Equilibrium: A Sign of Ruptured Aneurysm?

PURPOSE: Wall enhancement of saccular cerebral aneurysms has not been researched sufficiently. Our purpose of this study was to investigate the incidence of aneurysmal wall enhancement by the three-dimensional turbo spin-echo sequence with motion-sensitized driven equilibrium (MSDE-3D-TSE) imaging after gadolinium injection. METHODS: We retrospectively reviewed the pre- and postcontrast MSDE-3D-TSE images of 117 consecutive patients with intracranial aneurysms from September 2011 to July 2013. A total of 61 ruptured and 83 unruptured aneurysms of 61 patients with subarachnoid hemorrhage (SAH) and 56 non-SAH patients were enrolled in this study. We evaluated the wall enhancement of each aneurysm on postcontrast MSDE-3D-TSE images compared with precontrast images. We classified the aneurysmal wall enhancement into three groups as "Strong enhancement," "Faint enhancement," and "No enhancement." RESULTS: "Strong/Faint enhancement" of the aneurysm was detected in 73.8/24.6 % of the ruptured aneurysms and 4.8/13.3 % of the unruptured aneurysms. "No enhancement" was found in 1.6 % of the ruptured aneurysms and 81.9 % of the unruptured aneurysms. CONCLUSIONS: By magnetic resonance vessel wall imaging using the MSDE-3D-TSE sequence, wall enhancement was frequently observed on ruptured aneurysms. Therefore, aneurysmal wall enhancement may be an indicator of the ruptured condition, which is useful information for managing patients with SAH.

Diversity and Distribution of Rice Blast (Pyricularia oryzae Cavara) Races in Bangladesh.

The pathogenicity of 331 blast isolates (Pyricularia oryzae Cavara) collected from different regions and ecosystems for rice cultivation in Bangladesh was evaluated by compatibility on 23 differential varieties (DV), each harboring a single blast resistance gene, and susceptible 'Lijiangxintuanheigu' (LTH). A wide variation in virulence was found among the isolates, and 267 races were classified using a new designation system. Virulence of blast isolates against DV carrying the resistance genes Pia, Pib, Pit, Pik-s, Piz-t, Pi12(t), Pi19(t), and Pi20(t), as well as avirulence against those carrying Pish, Pi9, Pita-2, and Pita, was distributed widely in Bangladesh. Cluster analysis of the compatibility data on the DV initially classified the isolates into groups I and II. The virulence spectra of the two groups differed mainly according to the reactions of the DV to Pii, Pi3, Pi5(t), Pik-m, Pi1, Pik-h, Pik, Pik-p, and Pi7(t). Group I isolates were distributed mainly in rainfed lowlands, whereas group II isolates were found mainly in irrigated lowlands; however, there were no critical differences in geographic distribution of the blast isolates. In total, 26 isolates, which could be used to identify the 23 resistance genes of the DV on the basis of their reaction patterns, were selected as a set of standard differential blast isolates. To our knowledge, this is the first clear demonstration of the diversity and differentiation of blast races in Bangladesh. This information will be used to develop a durable blast protection system in that country.

Dynamic contrast-enhanced MRI of oral squamous cell carcinoma: a preliminary study of the correlations between quantitative parameters and the clinical stage.

OBJECTIVE: To probe the utility of dynamic contrast-enhanced MRI (DCE-MRI) parameters in assessing the clinical characteristics of oral squamous cell carcinoma. METHODS: A total of 85 tumours were included. We applied the Tofts and Kermode model for the DCE-MRI data and obtained three dependent parameters: the influx forward volume transfer constant into the extravascular extracellular space (EES) from the plasma (K(trans)), the fractional volume of EES per unit volume of tissue (ve) and the fractional volume of plasma (vp). We evaluated the correlations between these parameters and the clinical stages. RESULTS: The T stage showed a negative correlation with the K(trans) (r = -0.2272; p = 0.0365), but it did not show a significant correlation with the other parameters. The N stage showed a negative correlation with K(trans) (r = -0.1948; p = 0.0404), and there were significant differences between N1 and N2+3 (0.119 ± 0.027 vs 0.096 ± 0.023 min(-1); p = 0.0198) and between N0 and N2+3 (0.114 ± 0.29 vs 0.096 ± 0.023 min(-1); p = 0.0288). CONCLUSION: A decrease in the K(trans) at the primary site was found in advanced N stage cases, which might indicate that the hypoxic status cause a high possibility of the metastasis. ADVANCES IN KNOWLEDGE: A decrease in the K(trans) at the primary site suggested the high possibility of an advanced N stage.

Evaluation of diffusivity in the anterior lobe of the pituitary gland: 3D turbo field echo with diffusion-sensitized driven-equilibrium preparation.

BACKGROUND AND PURPOSE: 3D turbo field echo with diffusion-sensitized driven-equilibrium preparation is a non-echo-planar technique for DWI, which enables high-resolution DWI without field inhomogeneity-related image distortion. The purpose of this study was to evaluate the feasibility of diffusion-sensitized driven-equilibrium turbo field echo in evaluating diffusivity in the normal pituitary gland. MATERIALS AND METHODS: First, validation of diffusion-sensitized driven-equilibrium turbo field echo was attempted by comparing it with echo-planar DWI. Five healthy volunteers were imaged by using diffusion-sensitized driven-equilibrium turbo field echo and echo-planar DWI. The imaging voxel size was 1.5 × 1.5 × 1.5 mm(3) for diffusion-sensitized driven-equilibrium turbo field echo and 1.5 × 1.9 × 3.0 mm(3) for echo-planar DWI. ADCs measured by the 2 methods in 15 regions of interests (6 in gray matter and 9 in white matter) were compared by using the Pearson correlation coefficient. The ADC in the pituitary anterior lobe was then measured in 10 volunteers by using diffusion-sensitized driven-equilibrium turbo field echo, and the results were compared with those in the pons and vermis by using a paired t test. RESULTS: The ADCs from the 2 methods showed a strong correlation (r = 0.79; P < .0001), confirming the accuracy of the ADC measurement with the diffusion-sensitized driven-equilibrium sequence. The ADCs in the normal pituitary gland were 1.37 ± 0.13 × 10(-3) mm(2)/s, which were significantly higher than those in the pons (1.01 ± 0.24 × 10(-3) mm(2)/s) and the vermis (0.89 ± 0.25 × 10(-3) mm(2)/s, P < .01). CONCLUSIONS: We demonstrated that diffusion-sensitized driven-equilibrium turbo field echo is feasible in assessing ADC in the pituitary gland.

Engineering Au Nanoparticle Arrays on SiO2 Glass by Pulsed UV Laser Irradiation.

We study semi-regular arrays of Au nanoparticles (NP) obtained via UV laser irradiation of thin Au films on glass substrate. The NP structures are prepared from films of a thickness up to 60 nm produced by discharge sputtering or pulsed laser deposition, and annealed by nanosecond laser pulses at 266 or 308 nm, respectively, at fluencies in the range of 60-410 mJ/cm2. For the rare- and close-packed NP structures, consistent description of optical properties is derived from microscopic observation, measurements of the absorption, and Raman spectra, and modeling of the near-field intensity distributions. The absorption bands centered at 540-570 nm are ascribed to resonant absorption of the surface plasmons. For the band positions, half widths, and intensities, the dependence on the NP shape (partial spheres), size, size distribution, and also excitation energy is observed. The structures are characterized by markedly reduced dephasing times of ∼3 fs. It is shown, that laser annealing of thin Au films provides reliable and cost effective method for controlled preparation of semi-regular NP arrays favorable for photonic applications.

Efficacy of folinic acid in preventing oral mucositis in allogeneic hematopoietic stem cell transplant patients receiving MTX as prophylaxis for GVHD.

As the safety of folinic acid administration and its efficacy for reducing the toxicity of MTX remain controversial, we assessed the effect of folinic acid administration after MTX treatment for GVHD prophylaxis on the incidence of oral mucositis and acute GVHD. We retrospectively analyzed data for 118 patients who had undergone allogeneic hematopoietic SCT and had received MTX for GVHD prophylaxis. Multivariate analysis showed that systemic folinic acid administration significantly reduced the incidence of severe oral mucositis (odds ratio (OR)=0.13, 95% confidence interval (CI) 0.04-0.73, P=0.014). There was also a tendency for a lower incidence of severe oral mucositis in patients who received folinic acid mouthwash (OR=0.39, 95%CI 0.15-1.00, P=0.051). No significant difference was observed in the incidence of acute GVHD between patients who received systemic folinic acid administration and those who did not (P=0.88). Systemic folinic acid administration and mouthwash appear to be useful for reducing the incidence of severe oral mucositis in patients who have received allogeneic hematopoietic SCT using MTX as GVHD prophylaxis.

3D turbo spin-echo sequence with motion-sensitized driven-equilibrium preparation for detection of brain metastases on 3T MR imaging.

BACKGROUND AND PURPOSE: MSDE preparation is a technique for black-blood imaging. Our purpose was to evaluate the usefulness of a 3D TSE sequence with MSDE preparation in detecting brain metastases by comparing it with conventional sequences. MATERIALS AND METHODS: Postcontrast images of 227 patients who were suspected of having brain metastasis were prospectively obtained by using 3 T1-weighted 3D sequences: a gradient-echo sequence (MPRAGE), TSE-noMSDE, and TSE-MSDE. The number of visualized blood vessels and the lesion-to-normal CNR were compared among the 3 sequences. An observer test involving 9 radiologists was performed, and their diagnostic performance by using TSE-MSDE, MPRAGE, and combined TSE-MSDE and MPRAGE was compared by means of an FOM as an index of diagnostic performance derived by the JAFROC analysis, sensitivity, FP/case, and reading time. RESULTS: TSE-MSDE resulted in significantly better vessel suppression than the other 2 methods. TSE with and without MSDE resulted in significantly higher CNRs than MPRAGE. In the observer test, significantly higher sensitivity and FOM as well as significantly shorter reading time were achieved by TSE-MSDE compared with MPRAGE, but FP/case was significantly higher with TSE-MSDE. Combined TSE-MSDE/MPRAGE resulted in significantly higher sensitivity and FOM and similar FP/case and reading time compared with MPRAGE alone. CONCLUSIONS: With blood vessel suppression and increased CNR, TSE-MSDE improves radiologists' performances in detecting brain metastases compared with MPRAGE, but it may increase FP results. Combined with MPRAGE, TSE-MSDE achieves high diagnostic performance while maintaining a low FP rate.

Assessment of efficacy of a live oral poliovirus vaccine for virulent Sabin-like poliovirus 1 strains in Japan.

Virulent Sabin-like poliovirus (VSLP) was isolated from river and sewage waters between October 1993 and September 1995 in Toyama Prefecture, Japan (Yoshida et al., Lancet 356, 1461-1463, 2000). In this study, to assess the possibility of an epidemic of poliomyelitis caused by a VSLP in Japan under the current vaccination policy of administration of live attenuated oral poliovirus vaccine (OPV), we determined titers of serum neutralizing antibodies to poliovirus 1 (PV-1) strains Sabin (vaccine strain), Mahoney (wild-type strain) and G4-12 (VSLP) in various groups of residents of Toyama Prefecture, Japan. The seropositivity and geometric mean neutralizing antibody titers against these strains in the individuals who obtained two doses of OPV were 99.1%, 94.5% and 95.5%, respectively, and 564, 186 and 194, respectively. Although the antibody titers to G4-12 were lower compared with those to Sabin, these results indicate that the OPV vaccination policy in Japan has been effective in preventing poliomyelitis caused by VSLPs. These results also suggest that (i) an epidemic of poliomyelitis caused by a VSLP has not occurred in Japan due to herd immunity, and (ii) the possibility of reemergence of VSLPs will be prevented if sufficient herd immunity is acquired immediately after completion of the OPV vaccination in accordance with the poliomyelitis eradication program.

Effective in vivo purging with rituximab and autologous peripheral blood stem cell transplantation in a woman with CD5 positive primary cutaneous diffuse large B-cell lymphoma.

Generalized subcutaneous tumors developed without any other sites of the disease in a Japanese woman. Skin biopsy revealed CD5(+) and CD20(+) atypical diffuse large cells infiltrating subcutaneous tissues. The diagnosis was CD5(+) primary cutaneous diffuse large B-cell lymphoma. Tumor-specific PCR showed the existence of malignant cells in the peripheral blood and bone marrow. After three cycles of chemotherapy, she was remained in partial remission. Peripheral blood stem cells (PBSC) were harvested after the fourth cycles of chemotherapy combined with rituximab for in vivo purging. The contamination of tumor cells in PBSC was negative with PCR. She then underwent autologous peripheral blood stem cell transplantation using purged PBSC and has remained in complete remission for the past 24 month.

Localized relapse in bone marrow of extremities after allogeneic stem cell transplantation for acute lymphoblastic leukemia.

We report a patient with a relapsed in bone marrow of extremities after allogeneic peripheral blood stem cell transplantation for acute lymphoblastic leukemia (ALL). The patient complained of pain in the right upper arm and left leg 15 months after transplantation. Magnetic resonance imaging (MRI) and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) showed abnormal findings in bone marrow of upper and lower extremities. There were no findings of relapse in aspirates from the sternum and iliac bone marrow. Biopsy specimen from the iliac bone marrow showed normocellular marrow without leukemic cells. Biopsy specimen from the right humerus revealed marked leukemic cell infiltration in the bone marrow. This is apparently the first case of localized relapse of ALL in bone marrow of extremities. Physicians should be aware of unusual relapse sites of leukemia after allogeneic stem cell transplantation. MRI and FDG-PET may be of value in detecting this type of relapse.

Peripheral blood stem cell mobilization following CHOP plus rituximab therapy combined with G-CSF in patients with B-cell non-Hodgkin's lymphoma.

We mobilized peripheral blood stem cells (PBSC) following CHOP plus rituximab (CHOP-R) therapy, and compared with the findings following CHOP therapy without rituximab. All patients were given G-CSF starting from day 11 after CHOP therapy. Patients in the CHOP-R group (n=8) were given rituximab on day 12. Target CD34(+) cells number was collected in a single leukapheresis on day 14, from all the eight patients in the CHOP-R group. PBSC mobilization kinetics, CD34(+) cells yield and colony-forming ability in the graft collection, toxicity during mobilization, and engraftment after transplantation of CHOP-R group were not significantly different from those in the CHOP group (n=8). In all patients given CHOP-R therapy, CD20(+) cells and immunoglobulin heavy chain (IgH) rearrangement in the graft collection were undetectable by flow-cytometric analysis and Southern blot analysis, respectively, but with PCR analysis two of eight grafts were positive for IgH rearrangement. While further studies are needed to evaluate the efficacy of purging and the outcome of patients undergoing autologous transplantation, CHOP-R therapy can be safely and effectively used in the mobilization phase of PBSC collection, without excess clinical toxicity or deleterious effect on PBSC mobilization kinetics or engraftment time.

Successful treatment with rituximab for autoimmune hemolytic anemia concomitant with proliferation of Epstein-Barr virus and monoclonal gammopathy in a post-nonmyeloablative stem cell transplant patient.

A 30-year-old Japanese woman who underwent nonmyeloablative stem cell transplantation from her HLA-matched sister developed autoimmune hemolytic anemia (AIHA). There was proliferation of EBV-DNA in her peripheral blood and monoclonal gammopathy, both predictive factors of post-transplant lymphoproliferative disorder (PTLD). As conventional immunosuppressive therapy for AIHA could lead to overt PTLD, we decided to give her rituximab 375 mg/m(2) once weekly for a total of four doses. After this therapy, both her AIHA and monoclonal gammopathy were resolved and EBV-DNA became undetectable. Rituximab therapy deserves consideration for treatment of post-allogeneic stem cell transplant patients with AIHA, especially for patients who cannot be given immunosuppressive therapy.

Expression of pleiotrophin in hepatic nonparenchymal cells and preneoplastic nodules in carbon tetrachloride-induced fibrotic rat liver.

Pleiotrophin (PTN) is a heparin-binding protein, which induces growth, angiogenesis, differentiation, and transformation of cells. The aim of this study was to examine the role of PTN in liver fibrogenesis. Rats were treated with carbon tetrachloride (CCl4) for 3-9 weeks to induce liver fibrosis. The sirius-red staining of these liver tissue sections clearly showed the development of fibrosis and glutathione S-transferase placental type-positive preneoplastic nodules emerged at 7 weeks of the treatment. PTN expression was investigated in fibrotic liver tissues at the mRNA level using a real-time reverse transcription polymerase chain reaction and at the protein level by immunohistochemistry. Quantity of PTN mRNA increased 5-fold in fibrotic liver tissues at 7 weeks of CCl4-treatment over the control values. Immunohistochemistry localized PTN protein on hepatic nonparenchymal cells, mostly stellate cells and some of Kupffer cells, and the preneoplastic nodules in fibrotic liver tissues. PTN mRNA expression is significantly upregulated in the CCl4-induced chronic rat fibrotic liver tissues. We suggest that PTN might be involved in fibrogenesis and preneoplastic changes of liver.