Study design and patients
This was a retrospective study of 104 patients with CD and treated at the Ruijin Hospital between March 2015 and May 2016. The project was approved by the ethics committee of the Ruijin Hospital. The need for individual consent was waived because of the retrospective nature of the study.
All patients diagnosed with CD during the study period were included. The exclusion criteria were: (1) Poor MR image quality that could not be used for diagnosis and measurements; or (2) incomplete clinical data. The diagnosis of CD was based on the criteria from the World Health Organization (WHO). These criteria are: (1) Non-contiguous/segmental lesions visible by imaging, endoscopy, and/or the resected specimen; (2) manifesting as paving stones/longitudinal ulcer visible by imaging, endoscopy, and/or the resected specimen; (3) inflammatory lesions of the entire wall based on clinical manifestations and/or resected specimen showing abdominal masses, and stenosis visible by imaging and endoscopy; (4) histopathological manifestations of non-cheese-like granuloma; (5) cleft/fistula visible by imaging, endoscopy, and/or the resected specimen; and (6) anal lesions visible by clinical manifestations and/or biopsy/resected specimen. The diagnosis of CD is made in the presence of: (1) Criteria 1+2+3 and any one of 4, 5, or 6; or (2) criterion 4 and any two of 1, 2, or 3.
Endoscopic and MRI examinations were performed within 7 days. The disease course ranged from 1 to 5 years in all patients.
A first MRI and endoscopy were performed in the 104 included patients. According to the CDEIS score before treatment, the patients were classified as active CD (CDEIS > 6) or inactive CD (CDEIS ≤ 6). A second MRI and endoscopy were conducted in 61 active CD patients after 24-26 wk of medical therapy with glucocorticoids, infliximab (IFX), or adalimumab (ADA).
All patients were instructed to fast overnight prior to the MRI examination. The patients were requested to take polyethylene glycol electrolyte powder at 8 PM the day before MRI. Isotonic mannitol solution (2.5%; 2000 mL) was prepared by adding 250 mL of hyperosmotic mannitol solution (0.05 kg of mannitol, concentration of 20%) to 1750 mL of water. Each patient was given three to four 500-mL glasses of isotonic mannitol solution (total, 1500-2000 mL) to optimize the distention of the small bowel. Each glass was given within 10 min. The first glass was given at 40-45 min before MRI. All patients completed bowel preparation before MRI.
All MRI examinations were performed using a 1.5 T MRI unit (GE Signa, HDxt, GE Healthcare, Waukesha, WI, United States). Patients were placed in the supine position with an abdomen coil. MRI was performed with the following sequences: (1) Transverse fast imaging employing steady-state acquisition (FIESTA): Echo time/repetition time (TE/TR) 1.34/3.559 ms, slice thick/gap 5/1 mm, flip angle 55, bandwidth 125, number of excitation (NEX) 1.0, frequency (Freq) 224, field of view (FOV) 40 × 40 cm; (2) coronal T2 Weight Single-Shot Fast Spin Echo (T2WSSFSE): TE/TR 74.56/1800 ms, slice thick/gap 5/1 mm, bandwidth 31.25, Freq 288, FOV 40 cm × 40 cm; (3) coronal FIESTA: TE/TR 1.364/3.285 ms, slice thick/gap 5/1 mm, flip angle 55, bandwidth 125; (4) transverse diffusion weight imaging (DWI): b values were 0, 600 s/mm2, TE/TR 67.5/1800 ms, slice thick/gap 5/1 mm, Freq 128, NEX 2.0; and (5) coronal Liver Acquisition with Volume Acceleration (LAVA) dynamic enhanced scan: TE/TR 1.452/3.12 ms, slice thickness/gap 4-4.4/1 mm, flip angle 12, bandwidth 125, Freq 288, FOV 40 cm × 40 cm; contrast agent, Magnevist 0.2 mL/kg, injection rate of 2 mL/s, enhanced scan point of 20, 50, and 90 s after contrast agent injection.
All MR images were independently reviewed by two experienced gastrointestinal radiologists who were blinded to the CDEIS results. Since the CDEIS represents the worst segment seen during endoscopy, the radiologists selected the worst segment on MRI for analysis. In the present study, each lesion observed during MRI could be matched to the endoscopy findings.
T2WI can show the intestinal wall thickening, serosal edema (T2WI high signal), and mucosal defects suggesting ulcers[6-11,15]. For each individual, bowel thickness was measured using the T2WI sequence. Wall edema[6-11,15] (hyperintensity on T2WI of bowel wall relative to the signal of the psoas muscle), ulcer in mucosa (deep depression in the mucosal surface of a thickened segment), and reactive lymph nodes (enlarged > 1 cm) were observed in T2WI. LAVA dynamic enhanced sequence was used to evaluate[4,16]: (1) Wall enhancement pattern: layer stratified enhancement or non-layer stratified enhancement; (2) changes in morphology including shortened mesenteric border, pseudodiverticulum, and stenosis; and (3) perienteric exudation, wall edema, ulcer in mucosa, reactive lymph nodes, perienteric exudation, morphological changes, and layer stratified enhancement, each defined as present or absent.
For patients in the active phase, regions of interest (ROIs) of < 0.5-cm2 were placed on the mucous layer of the lesion segment. In active CD, the mucous layer can be seen clearly due to edema in the sub-mucous layer. For inactive CD, the ROI was placed on the whole bowel wall since the mucous and sub-mucous layers cannot be differentiated. According to a study by Semelka et al, quantitative measurement of ROIs of wall signal intensity (WSI) was conducted before and after intravenous contrast administration. Relative contrast enhancement (RCE) was calculated according to: RCE = (WSIpost-enhancement - WSIpre-enhancement)/(WSIpre-enhancement) × 100 × SDnoisepre-enhancement/SDnoise post-enhancement), where SDnoise pre-enhancement is the average of three standard deviations (SDs) of the signal intensity measured outside of the body before enhancement, and SDnoise post-enhancement presents the same noise after enhancement.
DWI can be used to measure the movement of water molecules in living bodies. In the presence of acute inflammation, the edema, exudation of intestinal wall tissue, and elevated inflammatory cytokine levels limit the movement of the water molecules in tissues and cells (i.e., the diffusion is limited). Hence, the DWI signals increase while apparent diffusion coefficient (ADC) values decrease. Those values are reversed when inflammation improves[6-11,15]. In DWI sequences, ROIs of ADC placed on the bowel wall of CD lesions were measured using the Functool Software, and the average values were obtained. A simplified Magnetic Resonance Index of Activity (MaRIA) was calculated for each segment using the formula 1.5 × wall thickness (mm) + 0.02 × RCE + 5 × edema + 10 × ulceration.
Artery enhancement sequence on T1W1 shows the blood supply of the intestine. aRCE is the enhancement rate during arterial phase and represents the degree of blood supply. pRCE is the blood supply during the portal phase. dRCE is the blood supply during the period of delay. In the presence of acute inflammation, the enhancement rates of the various phases are elevated. If the peak value of the enhancement curve is delayed, the inflammation is likely to be improved or chronic[6-11,15]. The average RCE (total RCE, tRCE; arterial phase RCE, aRCE; portal phase RCE, pRCE; delay phase RCE, dRCE) and ADC values of the lesions in each patient were obtained. ∆tRCE, ∆aRCE, ∆pRCE, ∆dRCE, ∆ADC, ∆MaRIA, ∆thickness, and ∆CDEIS were defined as ∆CDEIS = (indicators after treatment-indicators before treatment)/indicators before treatment.
If the lesions were improved after medical treatment of CD, the following MRI manifestations could be seen: (1) T2WI showed that the thickening of the intestinal wall was alleviated, edema was alleviated or had disappeared, and mucosal ulcers were healed; (2) dynamic T1W1 enhancement sequence showed that the enhancement of the lesion segment had weakened, and the intestinal wall was no longer stratified; (3) the exudation surrounding the intestines was reduced or had disappeared, and the enlarged lymph nodes surrounding the intestines had shrunk; and (4) DWI sequence showed that the signals of the diseased segment were reduced and ADC values were increased.