Introduction 1 2 3 4 4 5 6 7 8 9 10 11 12 1 13 16 17 19 20 27 Materials and methods Patients 1 Fig. 1 Flowchart of study design Endoluminal RF coil 29 1 Table 1 Imaging sequence parameters Sequence Repetition time (TR) Echo time (TE) Acquisitions Slice thickness (mm) Matrix Field of view (FOV) (mm) Pixel size (mm) T1-weighted TSE 551 14 2 4 512x512 200 0.39x0.39 T2-weighted TSE 3,520 70 2 3 1024x1024 220 0.21x0.21 T2-weighted GRE 1,050 35 1 3 512x512 220 0.43x0.43 T1-weighted GRE opposed phase 187 7 4 3 256x265 220 0.86x0.86 TSE GRE Image evaluation 30 T1: tumor invasion of the lamina propria of mucosa or invasion of submucosa, wall thickening, and signal intensity changes confined to these layers. T2: tumor invasion extended to the muscularis propria, and additional thickening through gastric layers with signal intensity changes showing either a homogeneous or inhomogeneous lesion without serosal abnormalities. If invasion extended beyond muscularis propria into an adjacent fat tissue plane without serosal infiltration, it was considered as T2. T3: tumor invasion of mucosa, submucosa, and muscularis propria, with infiltration of the serosa or changes in signal intensity presenting with micronodular strands as growth into extraserosal fat tissue. T4: tumor invasion into adjacent organs or structures clearly presenting as contiguous tumor extension or a mass with similar signal intensity as the gastric tumor. N staging was done counting the lymph nodes detectable on MRI, regarding them as pathologic due to their signal intensity. Since gastrectomy samples varied in lymph node content due to surgical technique and extension of the gastrectomy not comparable to an in vivo situation, N factor was graded into N+ for positive findings of lymph nodes and into N− for absence of lymph nodes. In each case, normal gastric wall features were assessed. Signal intensities of the mucosa, submucosa, muscularis propria, and serosa or subserosa were recorded, as well as the amount of layers in which the normal gastric wall could be differentiated into. A score system from 1 to 5 (1=poor; 5=very good) was used for several study items to weigh the power of their findings. Each sequence, for example, was rated for image quality on a range from 1 to 5, representing insufficient to very good. Signal intensity and morphology of the gastric tumors and demarcation to normal gastric wall were used to describe characteristics of tumor presentation. The lesion was identified by irregular architecture of gastric wall, abnormal thickening, and change in signal intensity of gastric wall layers, which usually present with sharp and clear demarcation into three to five different layers with distinct signal intensities and thickness. Tumor size was not measured, as it does not influence T staging or provide further information. Histopathology was considered the gold standard, and radiological data where compared with its results. All data are presented as absolute numbers and relatively as percentages. Concordance of histopathological results and radiological findings are reported as overall accuracy. Sensitivity, specificity, and accuracy for T factor, N+/− factor are provided. Detection rate of serous membrane invasion or the differentiation between T2 and T3 stages was assessed, as it defines advanced stages of disease. Ninety-five percent confidence intervals (CI) are given if statistically applicable. Results 29 Gastric tumor staging 2 3 4 5 6 Table 2 Comparison of histologic with endoluminal findings without knowledge of tumor region   Endoluminal magnetic resonance imaging (MRI) findings Histologic findings T1 T2 T3 T4 n T1 1 2 1 – 4 T2 1 7 7 – 15 T3 – 1 2 – 3 T4 – – 1 1 2 Table 3 Comparison of histologic findings with endoluminal findings acquired with knowledge of tumor region   Endoluminal magnetic resonance imaging (MRI) findings Histologic findings T1 T2 T3 T4 n T1 1 2 1 — 4 T2 1 13 1 — 15 T3 – 1 2 – 3 T4 – – – 2 2 Table 4 Sensitivity, specificity, and accuracy for each T stage; overstaging and understaging rates   T1 T2 T3 T4 Overall Sensitivity 1/4 13/15 2/3 2/2 – Specificity 19/20 6/9 19/21 22/22 – Accuracy 20/24 19/24 21/ 24 24/24 18/24 Overstaging 3/4 1/15 – – 4/24 Understaging – 1/15 1/3 – 2/24 Table 5 Results for serosal invasion detection Evaluation of serosal invasion Sensitivity 4/5 Specificity 17/19 Accuracy 21/24 False positive 2 Table 6 Signal intensities of gastric wall layers on T1-weighted, T2-weighted, and opposed-phase imaging from inside to outside   n a n a n a n b High – – Intermediate n b High Intermediate High Low High Low Intermediate Intermediate High n b High Intermediate – Low Low Intermediate Intermediate Low Low five layers (n=1)* – Intermediate – High Intermediate Low Intermediate a b n Nodal involvement Lymph node detection resulted in N+ for detected lymph nodes in 17 cases with N− in 7 cases. Sensitivity for detecting N+ was 71%±18.22, specificity 29%±18.07, and accuracy 58%±19.72. This reflects the limitation of the study design. Ex vivo gastrectomy specimens do not provide the same quantity of lymph nodes as pathological workup. The mean score rating N factor staging was 4.4 (range 2–5). Image analysis 6 6 3 4 2 Fig. 2a, b a b white arrowheads white arrows Fig. 3a, b white arrowhead a b black arrowheads a Discussion 20 31 20 31 20 21 28 32 20 28 20 33 34 35 34 36 33 37 38 An interesting learning point is reflected by the results of T staging. Knowledge of the gastric region where the tumor is located is important since T staging of the stomach depends on the gastric region. Tumors of the cardia and part of the fundus region where a serosal layer is missing are considered T2 whereas they would be T3 in other gastric regions. The study setup was intended to be as close as possible to a future in vivo setting with an MR endoscope, but tumor location and gastric region cannot be read on image data from gastrectomy specimens. An in vivo setting would enable investigators to acquire this information. After providing the tumors' gastric region, T staging accuracy improved to 75%. Thus, the gastric region of tumor location is an important fact for adequate staging of tumor invasion. While this study used an ex vivo model of gastric carcinomas and the amount of patients included could be higher, the entire range of T factors for gastric carcinomas is covered. Another limitation of this study is the missing congruence of lymph nodes present in the gastrectomy specimens due to surgical technique to those available for histopathology. This is reflected by N-factor staging results. An in vivo setting should be more accurate but poses new problems, such as motion artefacts due to patient or endoscope movement. Modern rapid MRI sequences and spasmolytic agents may be able to overcome these obstacles in an in vivo setting, but this is a goal for future studies. It is important to point out pitfalls of this imaging technique, as overstaging is a problem in many imaging modalities. Peritumor inflammation, micronodular affection of the serosal membrane, and diffuse-type gastric carcinoma were retrospectively identified as reasons for misinterpretation of tumor invasion. Overstaging occurred in 17%, with three T1 tumors not correctly classified. This is encouraging since all T1 tumors were detected as tumors but in two cases were classified as T2 tumors and one as T3. Only one incorrectly classified T2 tumor contributed to overstaging. This indicates that overstaging was not a problem of differentiation between T2 and T3 stages of disease. 2 3 2 4 Fig. 4a, b open arrows white arrows white arrowheads a black arrowheads b In this study, we have shown that our concept is functional and feasible for MRI of the stomach, and staging results comparable with other imaging modalities were achieved. Endoluminal MRI in combination with conventional MRI could assess local and regional imaging in one session, giving accurate information about local staging and metastatic spread of disease. Secondary contrast media should be evaluated for its use in improving gastric wall layer discrimination and identification as well as tumor demarcation. Additional studies are needed to assess the clinical feasibility of this coil concept in vivo for imaging of the upper gastrointestinal tract. High-resolution imaging of the pancreas could be another possible application. Today, most tumors of the stomach and esophagus are staged by conventional methods, such as endoscopy, EUS, or CT. Future prospects of endoscopic MRI may be limited to certain tumor entities, such as early or advanced carcinomas, but it could be able to answer additional specific clinical questions for relevant therapy decisions. Summary