MRI vs. Ultrasound for Suspected Appendicitis During Pregnancy

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1 JOURNAL OF MAGNETIC RESONANCE IMAGING 28: (2008) Original Research MRI vs. Ultrasound for Suspected Appendicitis During Pregnancy Gary M. Israel, MD, 1 * Nagina Malguria, MD, 1 Shirley McCarthy, MD, PhD, 1 Josh Copel, MD, 2 and Jeffrey Weinreb, MD 1 Purpose: To compare the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ultrasound (US) and MRI in evaluation of pregnant patients with a clinical suspicion of appendicitis. Materials and Methods: A total of 33 pregnant patients with suspected appendicitis underwent US and MRI. The original imaging reports generated at the time of presentation were used for data analysis. Pathology reports were used for disease confirmation in patients who underwent appendectomy. When surgery was not performed, a medical record review was performed. The sensitivity, specificity, PPV, and NPV were calculated for US and MRI in the diagnosis of appendicitis. Results: Five of the 33 patients had pathologically-proven appendicitis. Four of the five patients with appendicitis were correctly diagnosed at MRI while one was interpreted as indeterminate (appendix not seen). At US, one was correctly diagnosed, one was incorrectly diagnosed as normal, and three were interpreted as indeterminate (appendix not seen). In 13 patients, a normal appendix was diagnosed at MRI, none of whom had appendicitis. In three patients, a normal appendix was diagnosed at US, one of whom had appendicitis. When the appendix was visualized at MRI, the sensitivity, specificity, PPV, and NPV for the diagnosis of appendicitis was 100% for all parameters. When the appendix was visualized at US, the sensitivity, specificity, PPV, and NPV for the diagnosis of appendicitis was 50%, 100%, 100%, and 66%, respectively. Conclusion: Based on a relatively small number of truepositives, our data suggests that MRI is very useful for the diagnosis and exclusion of appendicitis in pregnant women. Key Words: appendicitis; pregnancy; magnetic resonance imaging; ultrasound J. Magn. Reson. Imaging 2008;28: Wiley-Liss, Inc. ACUTE APPENDICITIS OCCURS ONCE in approximately 1700 pregnancies and is the most common extrauterine indication for laparotomy in pregnancy (1). In some cases, this diagnosis may be straightforward at clinical presentation. However, in many cases, the clinical diagnosis of appendicitis in pregnancy is challenging since some of the hallmarks of appendicitis, such as nausea, vomiting, and abdominal pain, are often present in pregnant patients without appendicitis (1 3). In addition, fever may be absent in acute appendicitis and assessment of an elevated white blood count is difficult since pregnant patients may have a physiologic leukocytosis (1 3). Furthermore, physical examination may be unreliable and the location of the appendix variable, depending on the size of the gravid uterus, which may reposition the appendix within the peritoneal cavity (2 4). Since a delay in diagnosis leads to a significantly higher rate of maternal and fetal complications, accurate diagnosis of appendicitis in pregnancy is critical (1,2), and imaging can play a key role. Ultrasound (US) with a graded compression technique has long been considered the preferred imaging modality for the evaluation of appendicitis in pregnant patients since there is no exposure to ionizing radiation (5). Several recent studies have suggested that magnetic resonance imaging (MRI) is also useful and may be even more accurate than US in the diagnosis of acute appendicitis in pregnancy (3,6 8). However, there is limited data statistically comparing MRI and US findings. The purpose of this study was to compare the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of US and MRI in evaluation of pregnant patients with a clinical suspicion of appendicitis. 1 Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA. 2 Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut, USA. Current address for N.M.: Boston VA Healthcare System, Department of Radiology, 1400 VFW Parkway, West Roxbury, MA *Address reprint requests to: G.M.I., MD, Department of Diagnostic Radiology, Yale University School of Medicine, P.O. Box , 333 Cedar Street, New Haven, CT gary.israel@yale.edu Received January 3, 2008; Accepted April 29, DOI /jmri Published online in Wiley InterScience ( MATERIALS AND METHODS Research Plan and Subjects The Human Investigation Committee at our institution approved our retrospective study with waiver of informed consent. Between July 2004 and June 2006, 45 pregnant patients were referred for imaging to the department of radiology at Yale New Haven Hospital for a clinical suspicion of appendicitis. The decision to obtain imaging was made by the patient s primary care physician or the emergency room physician. Of these 2008 Wiley-Liss, Inc. 428

2 MRI vs. US for Appendicitis in Pregnancy patients, nine underwent US without MRI and three underwent MRI without US. The remaining 33 patients (age range: years, mean: 25.6 years, median: 24 years), underwent US followed by MRI within 12 hours, and constitute the study cohort. A total of 12 patients were in the first trimester, 16 in the second trimester, and five in the third trimester. Imaging Technique and Interpretation US Under the supervision of an attending radiologist certified by the American Board of Radiology, the US images were obtained by a US technologist and all images were reviewed by the radiologist before the patient left the US department. If the supervising radiologist felt further scanning was necessary, that radiologist performed the additional scanning. US was performed using a 5-MH to 10-MHz linear transducer, on either a Philips iu-22 or HDI 5000 unit using the graded compression technique described by Puylaert (9). US images were interpreted by one of 20 attending radiologists with full knowledge of the clinical findings. The 20 attending radiologists represent a combination of radiologists who cover the US service during routine daytime hours (8 AM 5 PM) and who cover the emergency room during after-hour shifts (5 PM 8 AM). The criteria for establishing the diagnosis of acute appendicitis was direct visualization of a noncompressible appendix with a diameter of 6 mm or more at the point of maximal tenderness with or without the presence of an appendicolith, surrounding inflammation, or abscess formation. The diagnostic criteria for negative findings on sonography were visualization of a normal compressible appendix less than 6 mm in diameter, with no evidence of inflammation, phlegmon, or abscess (10,11). US exams in which the appendix was not visualized were considered indeterminate. MRI For MRI, patients were imaged in the supine position without sedation, anesthesia, or intravenous or oral contrast. In all patients, a single-shot fast spin-echo (SSFSE) sequence (TR msec, TE, matrix size , slice thickness 5 mm, interslice gap 0.5 mm, field of view cm) in the axial, sagittal, and coronal planes through the abdomen and pelvis (localized to the right lower quadrant) was performed on a 1.5T MRI scanner (Signa; General Electric, Milwaukee, WI, USA). At the discretion of the interpreting attending radiologist, a fat-suppressed T2- weighted fast spin-echo (FSE) sequence (TR 5000 msec, TE 100 msec, number of excitations [NEX] 2, echo train length 16, matrix size , slice thickness 5 mm, interslice gap mm, field of view cm) was performed in the axial plane in 16 patients. In addition, five patients also underwent T1-weighted imaging in the axial plane. MR images were interpreted prospectively by one of five attending radiologists certified by the American Board of Radiology, with full knowledge of the clinical and US findings. On MRI, a normal appendix was diagnosed if the appendix measured 6 mm or less and was without wall thickening or periappendiceal fluid (12). Appendicitis was diagnosed when the appendiceal diameter was 7 mm and the lumen of the appendix was distended and fluid-filled and/or there was evidence of surrounding inflammation manifested by increased signal intensity of periappendiceal tissues on T2- weighted sequences (12). The appendix may or may not have contained appendicoliths (defined as focal low signal intensity filling defects on T2-weighted images). A nonvisualized appendix without inflammation or fluid in the expected location of the appendix was considered indeterminate. The patients original MRI and US reports generated at the time of presentation were used for data analysis. Any additional imaging findings mentioned in the reports that could explain the patients clinical condition were recorded for both US and MRI. Confirmation Each patient s medical record was reviewed. Final pathology reports were used for disease confirmation in patients who underwent appendectomy. For patients who did not undergo surgery, the medical records were evaluated for alternative diagnoses. Data Analysis and Statistics The sensitivity, specificity, PPV, and NPV were calculated for US and MRI in making or excluding the diagnosis of appendicitis. When available, surgical pathology results were the gold standard. For cases in which surgery was not performed, the medical record review was used as the gold standard. These calculations were first performed using cases in which the appendix was visualized at either US or MRI. The calculations were then recomputed to include cases in which the appendix was not visualized but no inflammatory changes were noted. In this instance, this constellation of findings was considered negative for appendicitis (7). RESULTS Patients With Appendicitis Of the 33 subjects, five patients (15%; 5/33) had pathologically-proven appendicitis, four of whom (12%, 4/33) had acute appendicitis and one of whom (3%; 1/33) had chronic appendicitis (Table 1). For the four patients with acute appendicitis, all were correctly diagnosed at MRI (Table 1, patients 2 5). At US, one patient was correctly diagnosed (in this patient, MRI was ordered after US by the referring physician to confirm the diagnosis) (Table 1, patient 2; Fig. 1); one patient was incorrectly diagnosed as normal (Table 1, patient 3; Fig. 2); and two patients were interpreted as indeterminate (appendix not seen) (Table 1, patients 4 and 5; Fig. 3). For the patient with chronic appendicitis, the appendix was not identified with either US or MRI (interpreted as indeterminate). At surgery, the tip of the appendix was found to be inflamed. At surgical pathology, there was no evidence of acute appendicitis, but fibrous oblit-

3 430 Israel et al. Table 1 Summary of Patients With Pathologically-Proven Appendicitis Patient number GA (weeks) US MRI Clinical outcome 1 28 Indeterminate for appendicitis Indeterminate for appendicitis Chronic appendicitis 2 26 Positive for appendicitis Positive for appendicitis (Fig. 1) Acute appendicitis with abscess 3 7 Negative for appendicitis Positive for appendicitis (Fig. 2) Acute appendicitis 4 6 Indeterminate for appendicitis Positive for appendicitis (Fig. 3) Acute appendicitis 5 24 Indeterminate for appendicitis Positive for appendicitis Acute appendicitis GA gestational age, US ultrasound. eration of the appendiceal lumen was noted, consistent with chronic appendicitis. Definitive Diagnoses at MRI In 13 patients (39%; 13/33), the MRI scans were interpreted as negative (a normal appendix was identified) and none of these patients were proven to have appendicitis upon medical record review. Therefore, a total of 17 patients (52%; 17/33) were definitively interpreted as either positive or negative for appendicitis at MRI. Indeterminate Diagnoses at MRI In 16 patients (48%; 16/33), the MRI was interpreted as indeterminate (an appendix was not identified). A total of 15 of these patients (94%, 15/16), did not have appendicitis upon medical record review. One of these patients (Table 1, patient 1), underwent surgery and was diagnosed with chronic appendicitis at surgical pathology. Definitive Diagnoses at US In three patients (9%; 3/33), the US exams were interpreted as negative (a normal appendix was present). In one of these three patients (33%; 1/3) (Table 1, patient 3), acute appendicitis was diagnosed at surgical pathology. For the remaining two patients, neither were proven to have appendicitis upon medical record review. The US results for four patients (12%; 4/33) were definitively interpreted as either positive or negative for appendicitis. Indeterminate Diagnoses at US In 29 patients (88%; 29/33), the US was interpreted as indeterminate (an appendix was not identified). In three of these patients (Table 1, patients 1, 4, and 5; 10%; 3/29), appendicitis was diagnosed at surgical pathology. A total of 26 of these patients (90%; 26/29), did not have appendicitis upon medical record review. Statistical Calculations When all cases are considered (including cases in which the appendix was not visualized but no inflammatory changes were noted) at MRI, the sensitivity was 80%, the specificity was 100%, the PPV was 100%, and the PPV was 97% for appendicitis. For US, the sensitivity was 20%, the specificity was 100%, the PPV was 100%, and the NPV was 88% for appendicitis. Figure 1. A 34-year-old female who is 26 weeks pregnant in whom acute appendicitis was correctly diagnosed with US and MRI. a: US examination performed of the right lower quadrant demonstrates a 9-mm noncompressible blind-ending tubular structure at the point of maximal tenderness, consistent with acute appendicitis. b: Coronal T2-weighted SSFSE (TR 2200 msec, TE 102 msec) MR image demonstrates mild distention of the appendix (thick arrows), which contains appendicoliths (thin arrow). The patient underwent laparoscopic appendectomy, and acute appendicitis was diagnosed at surgical pathology. The appendicoliths were confirmed at surgery.

4 MRI vs. US for Appendicitis in Pregnancy 431 At MRI, 17 patients (52%; 17/33) were definitively interpreted as either positive or negative for appendicitis without false-negative or false-positive results. The sensitivity, specificity, PPV, and NPV were all 100% in these patients. At US, four patients (12%; 4/33) were definitively interpreted as either positive or negative for appendicitis. For these four patients, the sensitivity was 50%, the specificity was 100%, the PPV was 100%, and the NPV was 66% for appendicitis. Nonappendiceal Findings In one patient in the third trimester of pregnancy, a normal appendix was identified at MRI. Multiple submucosal and intramural fibroids were present, some of which demonstrated increased signal on T1- and T2- weighted images. The possibility of infarction of those fibroids was raised, which correlated with the obstetrical outcome. Figure 2. A 20-year-old female who is seven weeks pregnant with acute appendicitis in whom a normal appendix was felt to be present at US but appendicitis was diagnosed at MRI. a: US examination performed of the right lower quadrant demonstrates a 5-mm tubular structure that was felt to represent a normal appendix. The patient underwent an MRI to evaluate for other causes of right lower quadrant pain. b: Axial T2- weighted SSFSE (TR 2200 msec, TE 102 msec) MR image demonstrate a fluid-filled distended appendix (thick arrows) measuring 1 cm and containing an appendicolith (thin arrow) consistent with acute appendicitis. A 2-cm fluid and gas collection (black arrow) is noted between the appendix and the right pelvic side wall, consistent with an abscess. c: Sagittal T2-weighted SSFSE (TR 2200 msec, TE 102 msec) MR image confirms the presence of a distended appendix (thick arrows) and appendicolith (thin arrow). At surgery, a perforated appendix was diagnosed. Figure 3. A 22-year-old female who is six weeks pregnant with acute appendicitis in whom the appendix was not seen at US but appendicitis was diagnosed at MRI. a,b: Consecutive coronal T2-weighted SSFSE (TR 2200 msec, TE 102 msec) MR images demonstrates a fluid-filled distended appendix (arrows in [a]) and multiple appendicoliths (arrows in ) consistent with acute appendicitis. This was confirmed at surgical pathology.

5 432 Israel et al. Two patients (6%; 2/33) were diagnosed with right ureteral calculi and secondary proximal hydroureteronephrosis at MRI. In one of these patients, the diagnosis was confirmed at ureteroscopy and she underwent stone removal and stent placement. In the second patient, urate crystals were found in her urine. US demonstrated absence of the right ureteral jet and, clinically, it was concluded that the patient had a ureteral calculus. The patient was treated with hydration and after three days the pain subsided, whereupon a repeat US exam demonstrated a right ureteral jet, consistent with passage of a ureteral calculus. Five patients (15%; 5/33) were found with right hydroureteronephrosis on MRI without an apparent etiology, which was assumed to represent physiologic hydronephrosis of pregnancy. There were no cases in which US suggested an alternative diagnosis. DISCUSSION CT and US are the imaging modalities of choice in nonpregnant patients with a clinical suspicion of appendicitis. Even though CT has been found to be reliable in the evaluation of appendicitis in pregnant patients (13), a recent study suggested that the radiation exposure during the exam may double the fetal risk for developing childhood cancer (14). Thus, there is reluctance to use CT during pregnancy for the evaluation of appendicitis, and as a result, US is often the initial imaging test (15). Previous studies evaluating US for diagnosing appendicitis in pregnancy have reported high sensitivity and specificity (5,16) and a low rate of nondiagnostic exams (5). Therefore, US is frequently used to evaluate for appendicitis in a pregnant patient and studies justifying its use are cited in the medical literature (17,18). Appendicitis can only be excluded with US when a normal appendix is identified; however, in 88% (29/33) of the US exams in our study, the appendix could not be identified, including three patients with pathologicallyproven appendicitis (two with acute and one with chronic appendicitis). These results are similar to those of Pedrosa et al (7) and Cobben et al (8) who found that 96% (44/46) and 92% (11/12), respectively, of US exams performed to evaluate for appendicitis in pregnancy were indeterminate due to a nonvisualized appendix. In contrast, Lim et al (5) found that only 7% (3/45) of US exams to evaluate for appendicitis in pregnancy were indeterminate. It is unclear why such a discrepancy exists, but perhaps US operator skill may be a factor. In our study, 20 different board certified radiologists interpreted the US studies and their differences in experience and expertise may have contributed to the number of indeterminate exams. Lim et al (5) did not specify the number or experience of the radiologists interpreting the exams. While it is possible that a small number of highly trained ultrasonographers interpreted those exams, this does not reflect typical current clinical practice of today, in which these exams are performed at any time of the day or night. The patient population may also have contributed to their results. In our study, only 36% (12/33) of the patients were in the first trimester as compared to 62% (28/45) of the patients in the study by Lim et al (5). The larger size of the gravid uterus during the later stages of pregnancy in our study may have hindered our ability to identify the appendix because the appendix has been shown to be displaced cephalad during the course of pregnancy (4). In addition, the number and size of the adnexal veins increase during pregnancy, which may make identifying the appendix more difficult. Also, the patients in the study by Lim et al (5) may have been thinner than the patients in our study, facilitating the evaluation for appendicitis with US. In contradistinction to our US results, the appendix was identified at MRI in 52% (17/33) of patients. While this represents a considerable improvement, it is less than the level reported by Pedrosa et al (7) and Oto et al (6), who identified the appendix in 83% (39/47) and 87 % (20/23) of pregnant patients at MRI, respectively. The reasons for this difference are unclear, but the use of oral contrast material in Pedrosa et al s (7) study and differences in pulse sequences, gestational age, and patient body habitus could account for some of these differences. The NPV of MRI in the evaluation of appendicitis in the pregnant patient is noteworthy. We found that when the appendix was identified, the NPV was 100%, as did Pedrosa et al (7). Since the clinical diagnosis of appendicitis in pregnancy is not straightforward, and the natural history of untreated appendicitis in most cases is perforation, there is a low threshold for the referring physician to order an imaging exam to exclude appendicitis, especially during pregnancy. While it is important to be able to accurately diagnose appendicitis accurately in pregnancy, it is equally useful to be able to exclude it. Therefore, the high NPV of MRI is appealing when considering the diagnostic imaging options. Finally, there is growing evidence that MRI is useful in evaluating for appendicitis in the nonpregnant patient. In a study by Nitta et al (12) of 37 nonpregnant patients with suspected appendicitis, 29 of 30 patients with acute appendicitis were correctly diagnosed with MRI. The remaining patient was diagnosed with cecal diverticulitis at surgery. In a different study by Incesu et al (19), 34 nonpregnant patients with acute appendicitis underwent MRI and US. In this study, MRI correctly diagnosed 33 of 34 cases (97%) of acute appendicitis as compared to US, which correctly diagnosed 26 of 34 cases (76%). Incesu et al (19) concluded that MRI was useful in the diagnosis of acute appendicitis and was more sensitive, more accurate, and had better NPV (with statistical significance) when compared to US. There are limitations to this study. Reports generated at the time of the original US or MRI were used for data collection and there may have been variability in the expertise of the radiologist interpreting each exam. This is especially true for the US exams in our study. Our radiology department provides around-the-clock emergency room coverage by a board-certified attending radiologist. These radiologists have varying levels of skill and expertise with US, which may have contributed to the overall inferior US results. Nonetheless, this does represent the general practice of radiology in our department and elsewhere. In addition, the MRI was performed after the US in all cases and the radiologist interpreting the MRI was

6 MRI vs. US for Appendicitis in Pregnancy 433 aware of the US results, which would introduce bias. Also, not all pregnant patients with suspected appendicitis underwent both US and MRI, thus some patients were excluded because they only underwent one exam. Finally, the total number of patients with appendicitis was small; however, there is increasing evidence that MRI performs better than US in the diagnosis or exclusion of appendicitis during pregnancy (3,6 8). In conclusion, our data suggests (based on a relatively small number of true-positives), that MRI is very useful for the diagnosis for appendicitis, with an excellent specificity, sensitivity, NPV, and PPV (all 100%) in the presence of a visualized appendix. The role of US in pregnant patients with a clinical suspicion of appendicitis is limited predominantly due to the large number of nondiagnostic exams. Because of its safety profile and availability, US will likely still continue to be performed in many venues but based on this and other studies (7,8), it will rarely be diagnostic. REFERENCES 1. Mourad J, Elliott JP, Erickson L, Lisboa L. Appendicitis in pregnancy: new information that contradicts long-held clinical beliefs. Am J Obstet Gynecol 2000;182: Stone K. Acute abdominal emergencies associated with pregnancy. Clin Obstet Gynecol 2002;45: Birchard KR, Brown MA, Hyslop WB, Firat Z, Semelka RC. MRI of acute abdominal and pelvic pain in pregnant patients. AJR Am J Roentgenol 2005;184: Oto A, Srinivasan PN, Ernst RD, et al. Revisiting MRI for appendix location during pregnancy. AJR Am J Roentgenol 2006;186: Lim HK, Bae SH, Seo GS. Diagnosis of acute appendicitis in pregnant women: value of sonography. AJR Am J Roentgenol 1992;159: Oto A, Ernst RD, Shah R, et al. Right-lower-quadrant pain and suspected appendicitis in pregnant women: evaluation with MR imaging initial experience. Radiology 2005;234: Pedrosa I, Levine D, Eyvazzadeh AD, Siewert B, Ngo L, Rofsky NM. MR imaging evaluation of acute appendicitis in pregnancy. Radiology 2006;238: Cobben LP, Groot I, Haans L, Blickman JG, Puylaert J. MRI for clinically suspected appendicitis during pregnancy. AJR Am J Roentgenol 2004;183: Puylaert JB. Acute appendicitis: US evaluation using graded compression. Radiology 1986;158: Poortman P, Lohle PN, Schoemaker CM, et al. Comparison of CT and sonography in the diagnosis of acute appendicitis: a blinded prospective study. AJR Am J Roentgenol 2003;181: Bau A, Atri M. Acute female pelvic pain: ultrasound evaluation. Semin Ultrasound CT MR 2000;21: Nitta N, Takahashi M, Furukawa A, Murata K, Mori M, Fukushima M. MR imaging of the normal appendix and acute appendicitis. J Magn Reson Imaging 2005;21: Ames Castro M, Shipp TD, Castro EE, Ouzounian J, Rao P. The use of helical computed tomography in pregnancy for the diagnosis of acute appendicitis. Am J Obstet Gynecol 2001;184: Hurwitz LM, Yoshizumi T, Reiman RE, et al. Radiation dose to the fetus from body MDCT during early gestation. AJR Am J Roentgenol 2006;186: Levine D. Obstetric MRI. J Magn Reson Imaging 2006;24: Barloon TJ, Brown BP, Abu-Yousef MM, Warnock N, Berbaum KS. Sonography of acute appendicitis in pregnancy. Abdom Imaging 1995;20: Ueberrueck T, Koch A, Meyer L, Hinkel M, Gastinger I. Ninety-four appendectomies for suspected acute appendicitis during pregnancy. World J Surg 2004;28: Patel SF, Reede DL, Katz DS, Subramaniam R, Amorosa JK. Imaging the pregnant patient for nonobstetric conditions: algorithms and radiation dose considerations. Radiographics 2007;27: Incesu L, Coskun A, Selcuk MB, Akan H, Sozubir S, Bernay F. Acute appendicitis: MR imaging and sonographic correlation. AJR Am J Roentgenol 1997;168: