Jonathan R. Dillman, MD, MSc. Associate Professor Department of Radiology Cincinnati Children s Hospital Medical Center
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1 MR Enterography in Children: Interpretation & Value-Added Jonathan R. Dillman, MD, MSc Associate Professor Department of Radiology Cincinnati Children s Hospital Medical Center
2 Disclosures Crohn s disease research funding from: Siemens Medical Solutions USA Bracco Diagnostics Use of gadolinium contrast agents for bowel imaging in children <2 years-old is off-label This talk would not be possible without the physicians, technologists, and patients of University of Michigan/C.S. Mott Children s Hospital
3 Objective To remind us how we can provide added-value when interpreting MR enterography (MRE) exams in pediatric Crohn s disease Added-Value = take a product generally considered homogeneous and provide a feature that gives it a greater sense of value
4 MRE: Added-Value 1. Establishing TRUE extent of disease Enteric, extra-enteric manifestations 2. Accurately assessing response to medical therapy 3. Detecting & characterizing bowel-related complications e.g., penetrating/stricturing disease
5 Value-Added MRE: True Extent of Disease Detection of proximal ileal/jejunal disease ( TI skipping ) Majority of GI tract NOT evaluable by endoscopy Lazarev et al. (Am J Gastroenterol 2013): Isolated in 6% Younger pts, more likely stricturing, more surgeries Incomplete ileocolonoscopy Dillman et al. (Pediatr Radiol 2011): 73% children with colonic Crohn s and incomplete colonoscopy had abnormal TI by MRE
6 Detection unexpected perianal disease Reported incidence in adults/children wide ranging Incidence 15% at diagnosis in children Unexpected pancreatobiliary abnormalities Sclerosing cholangitis/igg4-cholangiopathy Cholelithiasis Value-Added MRE: True Extent of Disease Pancreatitis (drug, autoimmune) Cholangiocarcinoma (rare)
7 Two Children with Newly Diagnosed Isolated Jejunal Crohn s Disease
8 16 year-old with Terminal Ileitis, Non-Diagnostic TI Biopsy
9 Unexpected Pancreatobiliary Disease Sclerosing Cholangitis Gallstones Cholangiocarcinoma Acute Pancreatitis
10 17 year-old, Untreated Crohn s Disease (4 Years) Jejunitis, ileitis, colitis, colonic stricture, gastrocolic fistula, perianal abscess
11 Value-Added MRE: Response to Medical Therapy Key Point: Bowel can appear very sick at MRI, while patient feels OK and labs are normal Only modest correlations between clinical, laboratory & radiologic markers of Crohn s activity
12 Bowel Wall Thickness vs. Fecal Calpro r = 0.58 Key Point: MRI and Labs only Modestly Correlate Dillman JR et al. Unpublished Data
13 MRI as a Biomarker: Therapeutic Response (Subjective) MRI provides assessment of therapy response Biomarker Numerous findings: Change in mural thickness, length of disease, mural edema, degree restricted diffusion, degree enhancement Nomenclature/Reporting Pseudopolyp/ulceration resolution Key Point: Opportunity for Standardized Less mesenteric inflammation/vasa recta engorgement Stricture resolution Penetrating complication resolution
14 16 year-old, Asymptomatic, No Response Baseline MRE 1 year later
15 14 year-old with Stricture, Near-Complete Response Baseline 1 year later
16 MRI as a Biomarker: Therapeutic Response (Objective) MRI disease activity score Example: Rimola J, et al. (Inflamm Bowel Dis 2011) MaRIA = 1.5(wall thickness) (RCE) + 5(edema) + 10(ulceration) Sum scores from 7 bowel segments (TI rectum) Overall score correlates with endoscopic (CDEIS) scoring (r=0.8; p< 0.001) ROC AUC for active disease = 0.93
17 MRI as a Biomarker: Therapeutic Response (Objective) Ordas et al. Gastroenterology 2014: MRE evaluates ulcer healing with a high level of accuracy when ileocolonoscopy is used as the reference standard. The MaRIA is a valid, responsive, and reliable index assessing response to therapy in patients with CD. MaRIA = 1.5(wall thickness) (RCE) + 5(edema) + 10(ulceration)
18 MRI as a Biomarker: Therapeutic Response (Objective) Diffusion-weighted imaging: Caruso A, et al. (Inflamm Bowel Dis 2014) DWI ADC value negatively correlates with Simple Endoscopic Score for CD (r = -0.63; p<0.0001) Hordonneau C, et al. (Am J Gastroenterol 2014) ADC < mm 2 /s sensitivity/specificity for active disease = 96.9% and 98.1% Reference standard = MaRIA score
19 MRI as a Biomarker: Therapeutic Response (Objective) DWI Key Points: Need More Longitudinal Data Concerning DWI Change in Response to Therapy Need More DWI/Histologic T1W+ Correlation ADC
20 Natural History of Infliximab Therapy? CRP Max Wall Thickness Bowel Remains Abnormal by MRI in 28 newly diagnosed pediatric Crohn s disease patients with terminal ileitis longitudinal follow-up Many Pts with Normal Lab Values Dillman JR et al. Unpublished Data
21 Value-Added MRE: Characterization of Strictures Intestinal strictures most often mixed, containing both inflammation and fibrosis (Adler J et al Inflamm Bowel Dis 2012; Rimola J et al. Am J Gastroenterol 2015) Critical unmet need: No current imaging method can directly detect/measure intestinal fibrosis or determine progression over time Do we know what severely fibrotic strictures look like at MRE?
22 U-M MRE Pediatric CD Stricture Data 23 surgically-resected TI strictures with correlative MRI ( ) Mean age = 16 years Median time from MRI surgery = 20 days Mean histologic fibrosis score (1-4): 3.52 Mean histologic inflammation score (1-4): 3.43 Spearman rho = 0.55 (p=0.006) No purely inflamed or purely fibrotic stricture! Dillman JR et al. Unpublished Data
23 U-M MRE Pediatric CD Stricture Data MRI vs. histology (N=23): Histologic fibrosis vs. upstream dilatation: ρ=0.74 What if upstream dilatation and SB feces both present? Histologic fibrosis vs. SB feces sign: OR = 7.5 (transmural vs. non-transmural fibrosis) No relationship OR = between 425; p< fibrosis and T2W SI or degree enhancement (transmural vs. non-transmural fibrosis) Aside: Co-existent penetrating complication in 52%! Dillman JR et al. Unpublished Data
24 17 year-old with Mixed Stricture Key Point: Severe Inflammation Does Not Preclude Extensive Fibrosis Histologic Scoring: Inflammation = 4, Fibrosis = 4
25 Gain of Enhancement & Fibrosis 70 sec 7 min
26 Conclusion Radiologists should attempt to maximize value delivered when interpreting/ reporting MRE exams Determine exact disease extent Assess response to therapy Characterize strictures as best possible Upstream dilatation, small bowel feces, delayed enhancement = fibrosis?
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