Tomomi Nobashi

Total lesion glycolysis as an IgG4-related disease activity marker

Abstract Objectives. 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) was reported to be useful for monitoring immunoglobulin G4-related disease (IgG4-RD); however, a quantitative FDG-PET/CT analysis such as total lesion glycolysis (TLG) has not yet been conducted. This study aimed to investigate whether TLG would correlate with serum markers in IgG4-RD, and the utility of TLG for disease monitoring. Methods. This retrospective study included 17 patients (12 men; median age, 62 years) who were followed up at Kyoto University Hospital and underwent FDG-PET/CT from April 2009 to November 2013. TLG was calculated for the involved lesions. Correlations between serum markers [IgG4, soluble IL-2 receptor (sIL-2R), lactate dehydrogenase (LDH), and C-reactive protein (CRP)] and TLG concomitant with FDG-PET/CT scans were investigated. Serial changes in TLG were assessed in patients who underwent follow-up FDG-PET/CT (n = 6). Results. The calculated median (IQL) TLG value was 154.8 (63.7–324.4). A significant correlation was found between the sIL-2R level and TLG (P = 0.001, rs = 0.763). In contrast, no correlations were found between the IgG4, LDH, or CRP levels and TLG. Increased or decreased TLG corresponded with clinical disease improvement or worsening. Conclusions. TLG correlated significantly with the serum sIL-2R level and may be useful for disease monitoring in IgG4-RD.

Prognostic value of fluorine-18 fludeoxyglucose positron emission tomography parameters differs according to primary tumour location in small-cell lung cancer

OBJECTIVE To investigate the prognostic value of fluorine-18 fludeoxyglucose (FDG) positron emission tomography (PET) parameters for small-cell lung cancer (SCLC), according to the primary tumour location, adjusted by conventional prognostic factors. METHODS From 2008 to 2013, we enrolled consecutive patients with histologically proven SCLC, who had undergone FDG-PET/CT prior to initial therapy. The primary tumour location was categorized into central or peripheral types. PET parameters and clinical variables were evaluated using univariate and multivariate analysis. RESULTS A total of 69 patients were enrolled in this study; 28 of these patients were categorized as having the central type and 41 patients as having the peripheral type. In univariate analysis, stage, serum neuron-specific enolase, whole-body metabolic tumour volume (WB-MTV) and whole-body total lesion glycolysis (WB-TLG) were found to be significant in both types of patients. In multivariate analysis, the independent prognostic factor was found to be stage in the central type, but WB-MTV and WB-TLG in the peripheral type. Kaplan-Meier analysis demonstrated that patients with peripheral type with limited disease and low WB-MTV or WB-TLG showed significantly better overall survival than all of the other groups (p < 0.0083). CONCLUSION The FDG-PET volumetric parameters were demonstrated to be significant and independent prognostic factors in patients with peripheral type of SCLC, while stage was the only independent prognostic factor in patients with central type of SCLC. ADVANCES IN KNOWLEDGE FDG-PET is a non-invasive method that could potentially be used to estimate the prognosis of patients, especially those with peripheral-type SCLC.

FDG uptake in less affected lung field provides prognostic stratification in patients with interstitial lung disease

This study evaluated the clinical significance of 18F-FDG PET/CT in patients with interstitial lung disease (ILD), by investigating the relationships between 18F-FDG PET/CT parameters and clinical indicators and by evaluating the prognostic implications of 18F-FDG PET/CT results. Methods: Ninety patients (51 men, 39 women; mean age, 55.4 y; age range, 26–78 y) with ILD who underwent 18F-FDG PET/CT were retrospectively analyzed. SUVmean was defined as the mean SUV of the less-affected lung field, SUVTF as adjusted SUVmean using tissue fraction (TF), and CTmean as the mean attenuation of the corresponding region of interest on high-resolution CT. SUVmean, SUVTF, and CTmean were compared in the 90 ILD patients and in 15 age- and sex-matched controls. Correlations of SUVmax, SUVmean, SUVTF, and CTmean with clinical indicators, including estimated percentage of forced vital capacity (%FVC), estimated percentage of diffusion capacity of the lungs for carbon monoxide (%DLco), sialylated carbohydrate antigen Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), C-reactive protein (CRP), lactate dehydrogenase (LDH), and ILD-sex-age-physiology (GAP) index, were evaluated using the Spearman rank correlation test and the Tukey–Kramer test. A Cox proportional hazards model was used for univariate and multivariate analyses of factors associated with lung transplantation-free survival. Results: SUVmean, SUVTF, and CTmean were significantly higher in ILD patients than in healthy controls, except for CTmean in patients with a nonusual interstitial pneumonia pattern. SUVmean and CTmean were significantly correlated with %FVC, %DLco, KL-6, and SP-D; SUVTF was significantly correlated with %DLco, KL-6, SP-D, and LDH; and SUVmax was weakly correlated with KL-6 and CRP. Univariate analysis showed that SUVmean, SUVTF, sex, %FVC, %DLco, KL-6, and ILD-GAP index were significantly prognostic of lung transplantation-free survival; and multivariate analysis showed that SUVmean and ILD-GAP index were independently prognostic of lung transplantation-free survival. A higher SUVmean indicated a poorer prognosis, especially in patients with moderate risk based on ILD-GAP index. Conclusion: SUVmean was significantly but moderately correlated with clinical indicators, providing independent prognostic information in patients with ILD. 18F-FDG PET/CT may be helpful for monitoring and risk stratification of ILD patients.

Evaluation of Tumor-associated Stroma and Its Relationship with Tumor Hypoxia Using Dynamic Contrast-enhanced CT and 18F Misonidazole PET in Murine Tumor Models

PURPOSE To determine the relationship between the fractional interstitial volume (Fis), as calculated at dynamic contrast material-enhanced (DCE) computed tomography (CT), and tumor-associated stroma and to analyze its spatial relationship with tumor hypoxia in several xenograft tumor models. MATERIALS AND METHODS All animal experiments were approved by the animal research committee. Mice with three different xenograft tumors (U251, CFPAC-1, and BxPC-3; n = 6, n = 8, and n = 6, respectively) underwent DCE CT then hypoxia imaging with fluorine 18 ((18)F) fluoromisonidazole (FMISO) positron emission tomography (PET) within 24 hours. Immunohistochemical analysis was performed in harvested tumors to detect hypoxia markers and to quantify microvascular and stromal density. Two DCE CT parameters (amount of interstitial space associated with the amount of stroma [Fis] and flow velocity [Fv]) were identified and quantitatively validated by using immunohistochemistry. FMISO uptake within the tumor was also assessed in relation to DCE CT parameters. Imaging and immunohistochemical parameters were assessed by using the Kruskal-Wallis test, Wilcoxon rank-sum test with Bonferroni correction, and Pearson correlation coefficient. RESULTS Almost no α-smooth muscle actin-positive cells were found in the U251 xenograft, while abundant stroma was found in the entire BxPC-3 xenograft and in the periphery of the CFPAC-1 xenograft. Quantitative analysis showed a significant correlation (R = 0.83, P < .0001) between Fis and stromal density. FMISO uptake had a negative correlation with Fis (R = -0.58, P < .0001) and Fv (R = -0.53, P < .0001). CONCLUSION DCE CT can be used to quantify parameters associated with tumor-associated stroma. Tumor hypoxia was Complementarily localized in tumor-associated stroma in these models.

A rigid and bioabsorbable material for anterior chest wall reconstruction in a canine model

OBJECTIVES The optimal material for anterior chest wall reconstruction following chest wall resection remains controversial. The aim of this experimental study was to evaluate short-term, morphological and histological outcomes of anterior chest wall reconstruction with a rigid and bioabsorbable material in a canine model. METHODS Twenty adult beagle dogs underwent anterior chest wall resection. In the experimental group (n = 10), the anterior chest wall was reconstructed with a rigid and bioabsorbable material composed of poly-L-lactide acid matrix (60 wt%) and uncalcined and unsintered hydroxyapatite particles (40 wt%), whereas in the control group it was (n = 10) reconstructed with dual polypropylene mesh sheets. Short-term complication rates were compared with a χ(2) test. Postoperative sternal deviations were evaluated with sternal alignment angles using computed tomography and multiplanar reconstruction and were compared with Mann-Whitney U-test immediately after reconstruction, and at 1, 3, 6, 9 and 12 months postoperatively. Histological findings of the regenerated chest wall tissue were obtained after staining with haematoxylin and eosin and Elastica van Gieson (EVG) and compared at 3, 6, 9 and 12 months. RESULTS There was not a significant difference in the short-term postoperative complication rate (P = 0.53) and the complication rate was 20% (wound infection, n = 1 and lethal mediastinitis, n = 1) in the control group and 10% (wound infection, n = 1) in the experimental group. The postoperative sternal deviation was significantly less remarkable at 1 month (123.3 ± 32.2° vs 159.4 ± 19.7°, P = 0.027), 3 months (109.8 ± 34.7° vs 150.9 ± 34.2°, P = 0.039) and 12 months (61 ± 15.6° vs 170.3 ± 6.6°, P = 0.046) in the experimental group than in the control group, whereas no significant difference was noted immediately after reconstruction (165.7 ± 6.4° vs 168.4 ± 9.1°, P = 0.50). Histological findings showed dense connective tissue in the regenerated chest wall in both groups and showed chondroblasts in the regenerated chest wall tissue at 3 and 6 months only in the experimental group. CONCLUSIONS Our results suggest that anterior chest wall reconstruction with a rigid and bioabsorbable material is feasible and may be a valuable alternative to reconstruction with a non-rigid and non-absorbable material.

Effects of diffusion time on non-Gaussian diffusion and intravoxel incoherent motion (IVIM) MRI parameters in breast cancer and hepatocellular carcinoma xenograft models

Background Perfusion-related intravoxel incoherent motion (IVIM) and non-Gaussian diffusion magnetic resonance (MR) parameters are becoming important biomarkers for differentiating malignant from benign tumors without contrast agents. However, diffusion-time dependence has rarely been investigated in tumors. Purpose To investigate the relationship between diffusion time and diffusion parameters in breast cancer and hepatocellular carcinoma xenograft mouse models. Material and Methods Diffusion-weighted MR images (DWI) were obtained on a 7-T magnetic resonance imaging (MRI) scanner at two different diffusion times (9.6 ms and 27.6 ms) in human breast cancer (MDA-MB-231) and hepatocellular carcinoma (HepG2 and PLC/PRF/5) xenograft mouse models. Perfusion-related IVIM (fIVIM and D*) and non-Gaussian diffusion (ADC0 and K) parameters were estimated. Parametric maps of diffusion changes with the diffusion times were generated using a synthetic apparent diffusion coefficient (sADC) obtained from b = 438 and 2584 s/mm2. Results ADC0 values significantly decreased when diffusion times were changed from 9.6 ms to 27.6 ms in MDA-MB-231, HepG2, and PLC/PRF/5 groups (P = 0.0163, 0.0351, and 0.0170, respectively). K values significantly increased in MDA-MB-231 and HepG2 groups (P < 0.0003 and = 0.0007, respectively); however, no significant difference was detected in the PLC/PRF/5 group. fIVIM values increased, although not significantly (P = 0.164–0.748). The maps of sADC changes showed that diffusion changes with the diffusion time were not homogeneous across tumor tissues. Conclusion Diffusion MR parameters in both breast cancer and HCC xenograft models were found to be diffusion time-dependent. Our results show that diffusion time is an important parameter to consider when interpreting DWI data.