Quantitative Image Analysis of Normal Reference Tissues and Tumors in TNE and VNE CT Images.

<p>Abbreviations: TNE, true nonenhanced, VNE, virtual nonenhanced; CT, computed tomography; ICC, intraclass correlation coefficient; HU, Hounsfield units.</p><p>Note. –Data are mean values ± standard deviation.</p>a<p>ICC was calculated for the intraclass correlations between VNE and TNE.</p><p><i>P</i> value denotes the statistical significance for ICC.</p><p>Quantitative Image Analysis of Normal Reference Tissues and Tumors in TNE and VNE CT Images.</p

T4b cancer correctly staged by single-phase protocol and mistakenly classified as T4a by dual-phase protocol in an 87-year-old female (BMI = 22.7).

<p>(A, B) VNE and TNE axial images show similar pictures of focal bowel wall thickening in the cecum with irregular outer margin and pericolonic fat infiltration into the visceral peritoneum (white arrow). (C, D) Axial view of iodine image and enhanced WA images during the portal venous phase show transmural enhancement of the tumor with irregular outer margin. Focal red-colored enhanced tumor direct invasion into the adjacent wall of the terminal ileum (white arrow) is well demonstrated on iodine image, but not visualize on the enhanced WA image. The preserved fat plane between the cancer and terminal ileum is erroneously interpreted on the enhanced WA image (white arrow). These findings suggest stage T4b by the single phase protocol and stage T4a by the dual phase protocol. An invasion of the terminal ileum was proved by the pathologic staging (pT4b).</p

Axial oblique MPR images of the colon in a 47-year-old man (BMI = 24.7) with T4a sigmoid colon cancer.

<p>(A, B) VNE and TNE images show similar pictures of focal bowel wall thickening in the sigmoid colon with irregular outer border and obvious pericolonic fat infiltration. (C, D) Iodine image and enhanced WA image during the portal venous phase show transmural enhancement of the sigmoid colon cancer with irregular outer border, enhanced pericolonic fat infiltration, and direct invasion to the adjacent visceral peritoneum (arrow). These findings suggest pathologic stage T4a.</p

Sagittal oblique MPR images of the rectosigmoid colon in a 65-year-old woman (BMI = 31.1) with T4b rectosigmoid colon cancer.

<p>(A, B) VNE and TNE images show similar pictures of annular bowel wall thickening (star) in the rectosigmoid colon. (C, D) Iodine image and enhanced WA image during the portal venous phase show marginal enhancement of rectosigmoid colon cancer (star) with direct invasion into the posterior wall of the uterus. These findings suggest pathologic stage T4b.</p

Image Quality of the TNE and VNE Images.

<p>Abbreviations: TNE, true nonenhanced, VNE, virtual nonenhanced; NA, non-appreciable.</p>a<p>Image quality is scaled as 1 to 5 (1 <i>excellent</i>, 2 <i>good</i>, 3 <i>fair</i>, 4 <i>poor</i>, 5 <i>noninterpretable</i>); image noise is scaled as 1 to 5 (1 <i>none</i>, 2 <i>minimal</i>, 3 <i>mild</i>, 4 <i>moderate</i>, 5 <i>severe</i>); image artifacts is scaled as 1 to 4 (1 indicating <i>none</i>, 2 <i>mild</i>, 3 <i>moderate</i>, 4 <i>severe</i>); level of acceptance is rated as 1 to 3 (1 <i>completely</i>, 2 <i>partially</i>, 3 <i>not</i> acceptable).</p>b<p>Kappa value denotes the agreement of image scoring between reader 1 and reader 2.</p><p>* denotes <i>P</i><0.05 for differences in qualitative scores between TNE and VNE, and for agreements of image scoring between reader 1 and 2.</p><p>Image Quality of the TNE and VNE Images.</p

Axial images of the colon in an 80-year-old man (BMI = 27.7) with T1-2 sigmoid colon cancer.

<p>(A, B) VNE and TNE images show similar pictures of focal bowel wall thickening (white circle) in the sigmoid colon with smooth outer border. (C, D) 50% iodine overlay image and enhanced WA image during the portal venous phase show transmural enhancement (white circle) of the sigmoid colon cancer and smooth outer border. These findings suggest pathologic stage T1-2.</p

Diagnostic Accuracy of Dual-phase and Single-phase CT Images for Each T Stage with Histopathologic Results as Reference Standard.

<p>Abbreviations: Dual-phase: Enhanced WA 120-kVp and TNE images; Single-phase: Iodine Overlay and VNE images.</p><p>Note.—Overall accuracy of T staging was 87.4% (90 of 103 neoplasms) with dual phase and 90.3% (93 of 103 neoplasms) with single phase CT images (<i>P</i> for difference: 0.507).</p>a<p>Data are numbers of neoplasms.</p>b<p>Kappa value denotes the agreement of pathological diagnosis between reader 1 and reader 2, and * denotes significant agreement (<i>P</i><0.05).</p><p>Diagnostic Accuracy of Dual-phase and Single-phase CT Images for Each T Stage with Histopathologic Results as Reference Standard.</p

Development of a Gd(III)-Based Receptor-Induced Magnetization Enhancement (RIME) Contrast Agent for β‑Glucuronidase Activity Profiling

β-Glucuronidase is a key lysosomal enzyme and is often overexpressed in necrotic tumor masses. We report here the synthesis of a pro receptor-induced magnetization enhancement (pro-RIME) magnetic resonance imaging (MRI) contrast agent ([Gd­(DOTA-FPβGu)]) for molecular imaging of β-glucuronidase activity in tumor tissues. The contrast agent consists of two parts, a gadolinium complex and a β-glucuronidase substrate (β-d-glucopyranuronic acid). The binding association constant (<i>K</i>_A) of [Gd­(DOTA-FPβGu)] is 7.42 × 10², which is significantly lower than that of a commercially available MS-325 (<i>K</i>_A = 3.0 × 10⁴) RIME contrast agent. The low <i>K</i>_A value of [Gd­(DOTA-FPβGu)] is due to the pendant β-d-glucopyranuronic acid moiety. Therefore, [Gd­(DOTA-FPβGu)] can be used for detection of β-glucuronidase through RIME modulation. The detail mechanism of enzymatic activation of [Gd­(DOTA-FPβGu)] was elucidated by LC-MS. The kinetics of β-glucuronidase catalyzed hydrolysis of [Eu­(DOTA-FPβGu)] at pH 7.4 best fit the Miechalis–Menten kinetic mode with <i>K</i>_m = 1.38 mM, <i>k</i>_cat = 3.76 × 10³, and <i>k</i>_cat/<i>K</i>_m = 2.72 × 10³ M^–1 s^–1. The low <i>K</i>_m value indicates high affinity of β-glucuronidase for [Gd­(DOTA-FPβGu)] at physiological pH. Relaxometric studies revealed that <i>T</i>₁ relaxivity of [Gd­(DOTA-FPβGu)] changes in response to the concentration of β-glucuronidase. Consistent with the relaxometric studies, [Gd­(DOTA-FPβGu)] showed significant change in MR image signal in the presence of β-glucuronidase and HSA. <i>In vitro</i> and <i>in vivo</i> MR images demonstrated appreciable differences in signal enhancement in the cell lines and tumor xenografts in accordance to their expression levels of β-glucuronidase