Monitoring tumor response to the vascular disrupting agent CKD-516 in a rabbit VX2 intramuscular tumor model using PET/MRI: Simultaneous evaluation of vascular and metabolic parameters

<div><p>Objectives</p><p>To determine whether the CKD-516 produces a significant change in vascular and metabolic parameters in PET/MRI</p><p>Materials and methods</p><p>With institutional Animal Care and Use Committee approval, 18 VX2 carcinoma tumors implanted in bilateral back muscles of 9 rabbits were evaluated. Serial PET/MRI were performed before, 4 hours after and 1-week after vascular disrupting agent, CKD-516 at a dose of 0.7 mg/kg (treated group, n = 10) or saline (control group, n = 8) administration. PET/MRI-derived parameters and their interval changes were compared between the treated and control group by using the linear mixed model. Each parameter within each group was also compared by using the linear mixed model.</p><p>Results</p><p>Changes of the volume transfer coefficient (K^trans) and the initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) in the treated group were significantly larger compared with those in the control group at 4-hour follow-up (mean, -39.91% vs. -6.04%, P = 0.018; and -49.71% vs. +6.23%, P = 0.013). Change of metabolic tumor volume (MTV) in the treated group was significantly smaller compared with that in the control group at 1-week follow-up (mean, +118.34% vs. +208.87%, P = 0.044). Serial measurements in the treated group revealed that K^trans and iAUC decreased at 4-hour follow-up (P < 0.001) and partially recovered at 1-week follow-up (P = 0.001 and 0.024, respectively). MTV increased at a 4-hour follow-up (P = 0.038) and further increased at a 1-week follow-up (P < 0.001), while total lesion glycolysis (TLG) did not show a significant difference between the time points. SUVmax and SUVmean did not show significant interval changes between time points (P > 0.05).</p><p>Conclusions</p><p>PET/MRI is able to monitor the changes of vascular and metabolic parameters at different time points simultaneously, and confirmed that vascular changes precede the metabolic changes by VDA, CKD-516.</p></div

Serial changes of PET/MRI parameters before and after the treatment with CKD-516.

<p>(a) Axial T2-weighted images demonstrated target tumors with high signal intensity in bilateral paravertebral muscles. (b) DCE-MRI revealed peripheral enhancement of tumors suggesting central necrosis. (c) K^trans map and (d) iAUC map demonstrated a reduction of values at 4 hours and partial recovery at 1 week follow-up. (e) PET images and (f) fusion images showed no significant differences of SUVmax or SUVmean.</p

Serial changes of PET/MRI parameters in control group.

<p>(a) Axial T2-weighted images demonstrated target tumors with high signal intensity in bilateral paravertebral muscles. At 1-week follow-up, there were areas of high signal intensity within tumors on T2 weighted images, suggestive of necrosis (arrows). (b) DCE-MRI, (c) K^trans map, (d) iAUC, (e) PET images and (f) fusion images.</p

Comparison of vascular and metabolic parameters between the control and treated groups at each time point and comparison of each parameter between time points in each group.

<p>Comparison of vascular and metabolic parameters between the control and treated groups at each time point and comparison of each parameter between time points in each group.</p

Serial measurement of (a) K^trans, (b) iAUC, (c) SUVmax, (d) SUVmean, (e) MTV and (f) TLG at different time points.

<p>* is a significant change compared to the baseline.</p> <p>K^trans: volume transfer coefficient</p> <p>iAUC: initial area under the gadolinium concentration-time curve until 60 seconds</p> <p>SUV: standardized uptake value</p> <p>MTV: metabolic tumor volume</p> <p>TLG: total lesion glycolysis.</p

Percentage changes of vascular and metabolic parameters compared with the baseline at each time point and P values of comparisons between the treated and control groups.

<p>Percentage changes of vascular and metabolic parameters compared with the baseline at each time point and P values of comparisons between the treated and control groups.</p

Value of Computerized 3D Shape Analysis in Differentiating Encapsulated from Invasive Thymomas

<div><p>Objectives</p><p>To retrospectively investigate the added value of quantitative 3D shape analysis in differentiating encapsulated from invasive thymomas.</p><p>Materials and Methods</p><p>From February 2002 to October 2013, 53 patients (25 men and 28 women; mean age, 53.94 ± 13.13 years) with 53 pathologically-confirmed thymomas underwent preoperative chest CT scans (slice thicknesses ≤ 2.5 mm). Twenty-three tumors were encapsulated thymomas and 30 were invasive thymomas. Their clinical and CT characteristics were evaluated. In addition, each thymoma was manually-segmented from surrounding structures, and their 3D shape features were assessed using an in-house developed software program. To evaluate the added value of 3D shape features in differentiating encapsulated from invasive thymomas, logistic regression analysis and receiver-operating characteristics curve (ROC) analysis were performed.</p><p>Results</p><p>Significant differences were observed between encapsulated and invasive thymomas, in terms of cystic changes (<i>p</i>=0.004), sphericity (<i>p</i>=0.016), and discrete compactness (<i>p</i>=0.001). Subsequent binary logistic regression analysis revealed that absence of cystic change (adjusted odds ratio (OR) = 6.636; <i>p</i>=0.015) and higher discrete compactness (OR = 77.775; <i>p</i>=0.012) were significant differentiators of encapsulated from invasive thymomas. ROC analyses revealed that the addition of 3D shape analysis to clinical and CT features (AUC, 0.955; 95% CI, 0.935–0.975) provided significantly higher performance in differentiating encapsulated from invasive thymomas than clinical and CT features (AUC, 0.666; 95% CI, 0.626–0.707) (<i>p</i><0.001).</p><p>Conclusion</p><p>Addition of 3D shape analysis, particularly discrete compactness, can improve differentiation of encapsulated thymomas from invasive thymomas.</p></div

An example of texture analysis of a persistent PSN.

<p>(A) Thin-section CT scan shows an 18 mm PSN (arrow) with fissural retraction in the right lower lobe in a 62-year-old male. (B) Texture analysis of the PSN shows high mean attenuation and low negative skewness (−305.5 Hounsfield units and −0.378, respectively). As this PSN was persistent, he underwent lobectomy and was diagnosed as having adenocarcinoma.</p

Clinical features in 77 Individuals with Transient and Persistent PSNs.

<p>Note: Except where indicated, data are numbers of individuals.</p><p>Data are means ± standard deviations.</p><p>Calculated with the independent sample <i>t</i> test.</p><p>Calculated with the Pearson <b>χ²</b> test.</p><p>Calculated with the Fisher exact test.</p><p>PSNs  =  part-solid nodules.</p

Interobserver variability of shape features of thymomas.

<p>Note—ICCs of less than 0.40 signifies poor agreement; 0.41–0.60, moderate agreement; 0.61–0.80, good agreement; and 0.81 or greater, excellent agreement.</p><p>^†ICC = intraclass correlation coefficients.</p><p>^††CI = confidence interval</p><p>Interobserver variability of shape features of thymomas.</p