JOURNAL OF MAGNETIC RESONANCE IMAGING 39:1518–1524 (2014)
Original Research
Diagnostic Performance of Diffusion-Weighted MR Imaging in Detecting Acute Appendicitis in Children: Comparison With Conventional MRI and Surgical Findings € €n Oral, MD,1 Mecit Kantarci, MD, PhD,1* Ummugulsum Bayraktutan, MD,1 Akgu Muhammet Demir, MD,3 Hayri Ogul, MD,1 Ahmet Yalcin, MD,1 Idris Kaya, MD,1 iter, MD,2 and Adnan Okur, MD1 Ahmet Bedii Salman, MD,2 Murat Yig Purpose: To determine the value of diffusion-weighted MRI for the diagnosis of acute appendicitis in children. Materials and Methods: Forty-five consecutive patients with a clinical diagnosis of acute appendicitis underwent abdominal MRI; 39 were operated on for acute appendicitis. First, the diffusion-weighted imaging (DWI) alone was reviewed, followed by conventional MRI alone, and then conventional MRI and DWI were reviewed by two observers within a consensus. The surgical findings were compared with the MRI. Sensitivity, specificity, and accuracy were calculated for DWI, conventional MRI, and combined DWI and conventional MRI for the depiction of acute appendicitis. Results: A combination of DWI and conventional MRI was the most sensitive and the most accurate, with corresponding sensitivity and accuracy of 0.92 and 0.92, respectively. Using DWI alone the sensitivity and accuracy was found to be 0.78 and 0.77, respectively. Using conventional MRI alone, sensitivity of 0.81 and accuracy of 0.82 was found for the consensus of the two observers. Conclusion: The use of combination of DWI and conventional MRI is a valuable technique in the diagnosis of acute appendicitis in children. Key Words: acute appendicitis; diffusion-weighted imaging; MRI J. Magn. Reson. Imaging 2014;39:1518–1524. C 2013 Wiley Periodicals, Inc. V
1 Ataturk University, School of Medicine, Department of Radiology, Erzurum, Turkey. 2 Ataturk University, School of Medicine, Department of Pediatric Surgery, Erzurum, Turkey. 3 Erzurum Region Education and Research Hospital, Department of Pediatric Surgery, Erzurum, Turkey. *Address reprint requests to: M.K., 200 Evler Mah. 14. Sok No 5, Dadaskent, Erzurum, Turkey. E-mail: [email protected] Received October 11, 2012; Accepted June 25, 2013. DOI 10.1002/jmri.24316 View this article online at wileyonlinelibrary.com. C 2013 Wiley Periodicals, Inc. V
ACUTE APPENDICITIS REMAINS the most common acute surgical condition of the abdomen and is the most commonly misdiagnosed condition in the pediatric age group (1). Although diagnosis and treatment have improved over time, appendicitis still continues to cause significant morbidity and remains a cause of death. However, with the usage of effective antibiotics, the mortality rate for complicated appendicitis has been close to zero, but still the cause of mortality is delayed diagnosis (2). In skilled hands, ultrasonography (US) has proved to be an effective diagnostic aid (1). Ultrasonography is the first choice radiological technique because it is a noninvasive, easily available, and rapid method with lack of ionizing radiation, although it has some limitations like operator-dependency, obesity, and retrocecal appendix location. Diagnostic accuracy with ultrasonography in identifying an inflamed appendix varies between 71% and 97% (3,4). Contrastenhanced CT is another technique for acute appendicitis diagnosis. However, ionizing radiation and the use of iodinated contrast medium are disadvantages, especially in pregnant women and children. MRI has become more widely used and does not require ionizing radiation and iodinated contrast media. Diffusion-weighted MRI is a noninvasive technique capable of probing the micro-environment of tissue by measuring water movement (5–7). The apparent diffusion coefficient (ADC) value in diffusionweighted imaging (DWI) determines the motion of water protons in the environment. If water molecules are restricted in their motion because of cell membranes or, in the case of free fluid, by high viscosity, the signal intensity is high. If water molecules can diffuse freely, the signal intensity is low (7). Diffusionweighted MRI has been increasingly used in the abdomen, and findings of DWI of different diseases (malignant or inflammatory processes) have been reported (8–10). To our knowledge, some reports have been published in the literature for detection of acute
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Table 1 Demographics and Clinical Features Parameter
Patients (n)
Age (mean) (years) Body mass index (mean) (kg/m2) Sex (M/F) Leukocyte (mean) (x103/mm3) Symptoms Abdominal pain located on RLQ Epigastric pain Diffuse abdominal pain Fever Vomitting Decreased appetite Physical examination RLQ tenderness RLQ guarding RLQ rebound Decreased bowel sound
7 (range: 0–14) 21 (range: 14–30) 27/18 13 (range: 6–20) 26 9 10 18 23 27 38 22 28 19
RLQ ¼ right lower quadrant.
appendicitis in adults with DW MR imaging (11–13). The aim of our study was to determine the accuracy of DWI for the diagnosis of acute appendicitis in children when added and compared with conventional MRI. We hypothesize that DWI will increase the sensitivity/accuracy for imaging diagnosis of acute appendicitis in children compared with conventional MRI alone.
MATERIALS AND METHODS Patients A total of 47 consecutive patients (mean age, 7; range, 0–14 years; 19 girls, 28 boys) with a clinical diagnosis of acute appendicitis and patients with suspected
acute appendicitis or appendix cannot be visualized on US were enrolled in this prospective study during a period of 4 months. The medical ethics committee of our hospital approved the study, and written consent of the parents was obtained before MRI examination. Two patients with claustrophobia were excluded. Ultrasonography was performed to 31 patients. A total of 45 patients had undergone MR imaging. The time range between the ultrasonography and MR imaging was 6–36 h. Thirty-nine of them were operated for acute appendicitis with a mean interval between surgery and MR imaging of 8 h. The remaining six of the patients did not undergo surgery after MR imaging. They were followed clinically over a period of 2 weeks to 2 months. Demographics and clinical features of patients are shown in Table 1. The study population was shown in Figure 1.
Imaging MRI MRI was performed with a 1.5 Tesla (T) body MRI (Magnetom Avanto, Siemens Healthcare) using an 18channel phased-array body coil. Before DWI, the subjects underwent a free-breathing axial and coronal turbo spin-echo T1-weighted sequence (repetition time [TR], 536 ms; echo time [TE], 11 ms; flip angle [FA], 150 ), axial and coronal fat-saturated turbo spin-echo T2-weighted sequence (TR, 5030 ms; TE, 101 ms; FA, 150 ), and an axial diffusion-weighted single-shot spin-echo echoplanar sequence with chemical shift-selective fat-suppression technique (TR/TE, 4900/93); matrix, 192 192; slice numbers, 30; slice thickness, 6 mm; interslice gap, 35%; field of view (FOV), 45 cm; averages, 5; acquisition time, approximately 3 min; PAT factor, 2; PAT mode,
Figure 1. Diagram demonstrating the patients and results. DWI ¼ diffusion-weighted imaging.
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Figure 2. An 11-year-old boy with a normal appendix. a: Axial TSE T2-weighted image showing the appendix. Arrow: appendix. b,c: Diffusion-weighted MR image of the appendix with b value of 400 s/mm2 and 800 s/mm2 showing hypointensity of the appendix. Arrow: appendix. d: ADC image showing hyperintensity of the appendix. ROI was placed on the appendix. ADC was 2.08 103 mm2/s. Arrow: appendix
parallel imaging with modified sensitivity encoding (mSENSE). Diffusion-weighted imaging was performed with b factors of 50, 400, and 800 s/mm2. All slices were acquired from diaphragm to the bottom of the pelvis. Oral and intravenous contrast material was not used. Twenty-six of the patients were sedated and the others did not need sedation for MRI. Imaging Analysis Two radiologists with 10 and 6 years of experience with abdominal MRI reviewed the MR examinations with consensus in an independent workstation (Leonardo console, software version 2.0; Siemens). First, the DW images, including the images with b values of 800 s/mm2 and ADC map were reviewed alone, followed by the conventional MR images, and finally the combined DW images and conventional MR images were reviewed together. This order of image review was kept constant to avoid any recall bias for the DW images, which were always reviewed first. The criteria for the diagnosis of acute appendicitis on MR imaging were thickening of the appendix (>6 mm in outer diameter), intraluminal fluid, and inflammation of the periappendiceal tissue, periappendiceal fluid collections, and markedly hyperintensity on DWI, hypointensity on ADC maps. ADC values were measured using three centrally placed regions of interest, (ROI)
the average value of the three ROIs was the accepted measurement. After a blinded review of the MR examinations, a comparison of the findings of DWI, conventional MRI, and combined DWI and conventional MRI was made with the reference standard was surgery. Statistical Analysis We used a McNemar’s test to analyze the diagnosis of acute appendicitis in children for DWI, conventional MRI, and combined DWI and conventional MRI. In all cases, a two tailed P value was determined, and the null hypothesis was rejected at P < 0.05.
RESULTS The study population and results were shown in Figure 1. Ultrasonography was performed in 31 patients. In 3 patients, ultrasonography findings were normal; in 13 patients, the appendix could not be visualized and the other patients suspected of acute appendicitis on US. Of the 45 patients who had undergone MR imaging with clinically suspected acute appendicitis and suspected acute appendicitis or appendix cannot be visualized on US, 39 patients (86%) were operated on. The remaining six patients, who had clinically
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Figure 3. An 11-year-old girl with acute appendicitis and fluid collection. a: Axial TSE T2-weighted image showing the appendix. Arrow: appendix, f: fluid. b,c: Diffusion-weighted MR image of the appendix with b value of 400 s/mm2 and 800 s/mm2 showing marked hyperintensity. Arrow: appendix; f: fluid. d: ADC image showing hypointensity of the appendix (marked restricted diffusion). ROI was placed on the appendix. ADC was 1.12 103 mm2/s. Arrow: appendix, f: fluid.
suspicious findings for acute appendicitis, were not referred for surgery. They were followed clinically over a period of 2 weeks to 2 months. Findings from followup examinations were unremarkable. In these patients, all imaging modalities showed negative findings for acute appendicitis. Histopathology revealed acute appendicitis in 36 of the operated patients (92%). Four patients had perforated appendicitis in surgery. Three patients had normal appendix in surgery. The operative results of them were the diagnoses of ovarian cyst rupture, Crohn’s disease and Meckel diverticulitis. There was apparently diffusion restriction in the periumblical area at the right lower quadrant in the patient with Meckel’s diverticulitis (1.07 103 mm2/s). In the other two patients, there was no any area showing diffusion restriction (mean ADC value of the appendix ¼ 2.17 6 0.11 103 mm2/s) (Fig. 2). DWI revealed the diagnosis of acute appendicitis in 28 patients (72%) (mean ADC value ¼ 1.12 6 0.17 103 mm2/s) (Figs. 3 and 4). In eight patients with appendicitis at surgery, DWI was negative for acute appendicitis. Three of them were negative for acute appendicitis also by using combined DWI and conventional MRI. In one of these patients, the appendix
could not be demonstrated on MRI but at surgery the appendix, which was located between the urinary bladder and anterior abdominal wall, was perforated. In the other three patients the greatest diameter of appendix was less than 5 mm. In the three patients who were negative for acute appendicitis on only DWI, there was appendicolith and wall thickening of the appendix without periappendiceal fluid or inflammation. In the remaining one patient, the diagnosis was only mesenteric lymphadenitis on DW MRI. Table 2 shows the results of imaging modalities in the diagnosis of acute appendicitis by observers’ consensus. The combination of DWI and conventional MRI was the most sensitive and the most accurate method, depicting 33 cases of acute appendicitis, with corresponding sensitivity and accuracy of 0.92 (P < 0.05). Using DWI alone, observers depicted and localized 28 cases of acute appendicitis (sensitivity: 0.78; and accuracy: 0.77), whereas conventional MRI depicted and localized 29 cases of acute appendicitis (sensitivity: 0.81; and accuracy: 0.82). A case that was misidentified as acute appendicitis (false positive) in DWI was a case of inflamed Meckel’s diverticulum, which was found on surgery.
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Figure 4. An 8-year-old boy with acute appendicitis. a: Axial TSE T2-weighted image showing the appendix (arrow). b,c: Diffusion-weighted MR image of the appendix (arrow) with b value of 400 s/mm2 and 800 s/mm2 showing marked hyperintensity. d: ADC image showing hypointensity of the appendix (marked restricted diffusion). ROI was placed on the appendix (arrow). ADC was 0.97 103 mm2/s.
The McNemar’s Test of Correlated Proportions The combination of DWI and conventional MRI was most sensitive and accurate for acute appendicitis compared with DWI alone (P < 0.05) and conventional MRI alone (P < 0.05) for observers’ consensus. There was no significant difference DWI and conventional MRI (P > 0.05).
DISCUSSION Acute appendicitis is the most common cause of abdominal surgical emergency in children. Although physical examination, laboratory tests, and patient’s history improve the diagnosis, the negative laparotomy
rate is high especially in female patients (14). Further evaluation with radiological techniques like ultrasonography, computed tomography, and MRI is required for minimizing negative laparotomy rates, delayed surgery, and probable complications of perforation. Ultrasonography is an easily available and performed technique in the diagnosis of acute appendicitis with a lack of ionizing radiation. Sonographer-dependency, acute appendicitis with retrocecal location, and obesity are the disadvantages of this method. In these cases, CT is recommended with a sensitivity and specifity of more than 90% (14–17). However, ionizing radiation and the use of iodinated contrast media are disadvantages, and CT is not preferred especially in pregnant women and children (18).
Table 2 Results of Imaging Modalities in the Diagnosis of Acute Appendicitis by the Consensus of Two Observers According to the Histopathological Findings Type of imaging
TP
FN
TN
FP
Sensitivity
Specificity
Accuracy
DWI Conventional MRI Combined MRI
28 29 33
8 7 3
2 3 3
1 0 0
0,78 0,81 0,92
0,67 1,0 1,0
0,77 0,82 0,92
TP ¼ true positive; FN ¼ false negative; TN ¼ true negative; FP ¼ false positive.
DW-MRI in Acute Appendicitis in Children
MRI has become a widely used method with an avoidance of ionizing radiation especially in children and females. It has some disadvantages like long examination time, high cost, and difficulty in claustrophobic patients. Incesu et al. found sensitivity and accuracy of MR imaging in the diagnosis of acute appendicitis to be 97% and 95%, respectively (19). However, in this study fat-suppressed and gadoliniumenhanced MR imaging is recommended. Another study showed that unenhanced turbo spin echo and fatsuppressed images provide accurate diagnosis of acute appendicitis (20). Sensitivity and accuracy of MR imaging in the above-mentioned studies are higher than the present study which might be elucidated with gadolinium use and age of study population. Diffusion-weighted MR imaging is well-established in the setting of acute cerebral infarct and has been more recently shown to help some abdominal diseases. It has been used in abdominal and pelvic oncologic MRI and in inflammatory diseases, such as acute-chronic pancreatitis, renal infections, hepatitis, and liver fibrosis and inflammatory bowel disease (21). This method uses pulse sequences and techniques that are sensitive to very small-scale motion of water protons at the microscopic level (6,7). Inci et al evaluated the utility of DW MRI in the diagnosis of acute appendicitis in adults (11). In this study, the sensitivity and specificity of DW MR imaging for diagnosis of acute appendicitis were found to be 98.7% and 100%, respectively. In our study, we compared the performance of DWI and combined imaging in the evaluation of acute appendicitis in children. For observers’ consensus, the sensitivity was 78% and accuracy was 77%, by using DWI alone. The sensitivity was 81% and accuracy was 82%, by using conventional MRI alone. When DW images were added to conventional MRI sequences, both the sensitivity and accuracy increased (sensitivity: 0.92 and accuracy: 0.92). Relatively poor spatial resolution and increased anatomic distortion of DWI especially in small size of pediatric patients and small number of patients may explain the difference between values of these two studies. They found mean ADC value of inflamed appendix as 1.22 6 0.18 103 mm2/s and 2.02 6 0.19 103 mm2/s of normal appendix similar to ours. Combined DWI and conventional MRI missed only three patients which were surgery proven acute appendicitis. The greatest diameter of the appendix in the two patients was less than 5 mm. The diagnosis of the other one was perforated appendicitis localized between urinary bladder and anterior abdominal wall. Furthermore, two patients were interpreted as not to have appendicitis in imaging sessions but diagnosed as ovarian cyst rupture and Crohn’s disease in surgery. There was one false positive result with DWI. This patient had an inflamed Meckel’s diverticulum found on surgery. In another study, the effectiveness of DW-MRI and ADC values in the diagnosis of acute appendicitis and differentiation of perforated and nonperforated appendicitis cases, with histopathological correlation were evaluated (12). In that study, the sensitivity, specificity, positive predictive value, negative predictive value,
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and accuracy rate of DW-MRI in the diagnosis of acute appendicitis were 97.5%, 100%, 97.5%, 100%, and 98.1%, respectively. The lower results of our study may be explained by the pediatric age group. They found mean ADC value in patients with acute appendicitis (1.01 6 0.26 103 mm2/s) similar with us. Our study has some limitations. One of them is the relatively small number of patients. Larger groups are needed for the evaluation of acute appendicitis with MRI. Second, there was a lack of intravenous and enteric contrast material, which plays an important role in detecting wall enhancement of inflamed appendix and intestine. Third, not only inflammatory diseases but the various other pathologies of this region should be studied with larger groups. Fourth, most of US examinations were done at outside of our center, thus we did not take into account US findings in this study. The inevitable waiting time for MRI—which had not led to any ascribable complications such as perforation or aggravated pain on follow-up in our study— besides requiring skill to assess and not availability in all centers are disadvantages of MRI. In conclusion, diffusion-weighted MR imaging technique is noninvasive, does not require ionizing radiation or injection of contrast material, and can be easily added to an MR examination protocol because it requires only a short time for the examination. This study showed that if DWI is added to the conventional MR imaging, diagnostic accuracy of the imaging method increases for the depiction of acute appendicitis with MRI in pediatric patients with clinical suspicion. Accordingly, diffusion-weighted MR imaging significantly improves the diagnosis of acute appendicitis in our population of children. ACKNOWLEDGMENTS This article was presented as an oral presentation at the ECR 2012 European Congress of Radiology, March 1–5, 2012, in Vienna, Austria. REFERENCES 1. Dunn JCY, Grosfeld JL. Appendicitis pediatric surgery, 6th edition. Chapter 98. Philadelphia, PA: Mosby; 2006. p 1501. 2. Neuspiel DR, Kuller LH. Fatalities from undetected appendicitis in early childhood. Clin Pediatr 1987;26:573–575. 3. Wilson EB, Cole JC, Nipper ML, et al. Computed tomography and ultrasonography in the diagnosis of appendicitis: when are they indicated? Arch Surg 2001;136:670–675. 4. Rao PM, Boland GW. Imaging of acute right lower abdominal quadrant pain. Clin Radiol 1998;53:639–649. 5. Vandecaveye V, De Keyzer F, Vander Poorten V, et al. Evaluation of the larynx for tumour recurrence by diffusion weighted MRI after radiotherapy: initial experience in four cases. Br J Radiol 2006;79:681–687. 6. Le Bihan D, Turner R, Douek P, Patronas N. Diffusion MR imaging: clinical applications. AJR Am J Roentgenol 1992;159:591–599. 7. Le Bihan D. Diffusion, perfusion and functional magnetic resonance imaging. J Mal Vasc 1995;20:203–214. 8. Koh DM, Collins DJ. Diffusion-weighted MRI in the body: applications and challenges in oncology. AJR Am J Roentgenol 2007; 188:1622–1635. 9. Yoshikawa T, Kawamitsu H, Mitchell DG, et al. ADC measurement of abdominal organs and lesions using parallel imaging technique. AJR Am J Roentgenol 2006;187:1521–1530.
1524 10. Onur MR, Poyraz AK, Kocakoc E, et al. Diagnosis of peritoneal metastases with abdominal malignancies: role of ADC measurement on diffusion weighted MRI. Eurasian J Med 2012;44:163– 168. 11. Inci E, Kilickesmez O, Hocaoglu E, Aydin S, Bayramoglu S, Cimilli T. Utility of diffusion-weighted imaging in the diagnosis of acute appendicitis. Eur Radiol 2011;21:768–775. € D€ 12. Avcu S, C¸etin FA, Arslan H, Kemik O, ulger AC. The value of diffusion-weighted imaging and apparent diffusion coefficient quantification in the diagnosis of perforated and nonperforated appendicitis. Diagn Interv Radiol 2013;19:106–110. 13. Leeuwenburgh MM, Wiarda BM, Bipat S, et al. Acute appendicitis on abdominal MR images: training readers to improve diagnostic accuracy. Radiology 2012;264:455–463. 14. Curtin KR, Fitzgerald SW, Nemcek AA, Hoff FL, Vogelzang RL. CT diagnosis of acute appendicitis: imaging findings. AJR Am J Roentgenol 1995;64:905–909. 15. Balthazar EJ, Birnbaum BA, Yee J, Megibow AJ, Roshkow J, Gray C. Acute appendicitis: CT and US correlation in 100 patients. Radiology 1994;190:31–35.
Bayraktutan et al. 16. Malone AJ, Wolf CR, Malmed AS, Melliere B. Diagnosis of acute appendicitis: value of unenhanced CT. AJR Am J Roentgenol 1993;60:763–766. 17. Friedland JA, Siege MlJ. CT appearance of acute appendicitis in childhood. AJR Am J Roentgenol 1997;168:439–442. 18. Thirumoorthi AS, Fefferman NR, Ginsburg HB, Kuenzler KA, Tomita SS. Managing radiation exposure in children-reexamining the role of ultrasound in the diagnosis of appendicitis. J Pediatr Surg 2012;47:2268–2272. 19. Incesu L, Coskun A, Selcuk MB, Akan H, Sozubir S, Bernay F. Acute Appendicitis: MR Imaging and Sonographic Correlation. AJR Am J Roentgenol 1997;168:669–674. 20. H€ ormann M, Paya K, Eibenberger K, et al. MR Imaging in children with nonperforated acute appendicitis: value of unenhanced MR imaging in sonographically selected cases. AJR Am J Roentgenol 1998;171:467–470. 21. Yagci AB, Ozari N, Aybek Z, Duzcan E. The value of diffusionweighted MRI for prostate cancer detection and localization. Diagn Interv Radiol 2011;17:130–134.
Original Research
Diagnostic Performance of Diffusion-Weighted MR Imaging in Detecting Acute Appendicitis in Children: Comparison With Conventional MRI and Surgical Findings € €n Oral, MD,1 Mecit Kantarci, MD, PhD,1* Ummugulsum Bayraktutan, MD,1 Akgu Muhammet Demir, MD,3 Hayri Ogul, MD,1 Ahmet Yalcin, MD,1 Idris Kaya, MD,1 iter, MD,2 and Adnan Okur, MD1 Ahmet Bedii Salman, MD,2 Murat Yig Purpose: To determine the value of diffusion-weighted MRI for the diagnosis of acute appendicitis in children. Materials and Methods: Forty-five consecutive patients with a clinical diagnosis of acute appendicitis underwent abdominal MRI; 39 were operated on for acute appendicitis. First, the diffusion-weighted imaging (DWI) alone was reviewed, followed by conventional MRI alone, and then conventional MRI and DWI were reviewed by two observers within a consensus. The surgical findings were compared with the MRI. Sensitivity, specificity, and accuracy were calculated for DWI, conventional MRI, and combined DWI and conventional MRI for the depiction of acute appendicitis. Results: A combination of DWI and conventional MRI was the most sensitive and the most accurate, with corresponding sensitivity and accuracy of 0.92 and 0.92, respectively. Using DWI alone the sensitivity and accuracy was found to be 0.78 and 0.77, respectively. Using conventional MRI alone, sensitivity of 0.81 and accuracy of 0.82 was found for the consensus of the two observers. Conclusion: The use of combination of DWI and conventional MRI is a valuable technique in the diagnosis of acute appendicitis in children. Key Words: acute appendicitis; diffusion-weighted imaging; MRI J. Magn. Reson. Imaging 2014;39:1518–1524. C 2013 Wiley Periodicals, Inc. V
1 Ataturk University, School of Medicine, Department of Radiology, Erzurum, Turkey. 2 Ataturk University, School of Medicine, Department of Pediatric Surgery, Erzurum, Turkey. 3 Erzurum Region Education and Research Hospital, Department of Pediatric Surgery, Erzurum, Turkey. *Address reprint requests to: M.K., 200 Evler Mah. 14. Sok No 5, Dadaskent, Erzurum, Turkey. E-mail: [email protected] Received October 11, 2012; Accepted June 25, 2013. DOI 10.1002/jmri.24316 View this article online at wileyonlinelibrary.com. C 2013 Wiley Periodicals, Inc. V
ACUTE APPENDICITIS REMAINS the most common acute surgical condition of the abdomen and is the most commonly misdiagnosed condition in the pediatric age group (1). Although diagnosis and treatment have improved over time, appendicitis still continues to cause significant morbidity and remains a cause of death. However, with the usage of effective antibiotics, the mortality rate for complicated appendicitis has been close to zero, but still the cause of mortality is delayed diagnosis (2). In skilled hands, ultrasonography (US) has proved to be an effective diagnostic aid (1). Ultrasonography is the first choice radiological technique because it is a noninvasive, easily available, and rapid method with lack of ionizing radiation, although it has some limitations like operator-dependency, obesity, and retrocecal appendix location. Diagnostic accuracy with ultrasonography in identifying an inflamed appendix varies between 71% and 97% (3,4). Contrastenhanced CT is another technique for acute appendicitis diagnosis. However, ionizing radiation and the use of iodinated contrast medium are disadvantages, especially in pregnant women and children. MRI has become more widely used and does not require ionizing radiation and iodinated contrast media. Diffusion-weighted MRI is a noninvasive technique capable of probing the micro-environment of tissue by measuring water movement (5–7). The apparent diffusion coefficient (ADC) value in diffusionweighted imaging (DWI) determines the motion of water protons in the environment. If water molecules are restricted in their motion because of cell membranes or, in the case of free fluid, by high viscosity, the signal intensity is high. If water molecules can diffuse freely, the signal intensity is low (7). Diffusionweighted MRI has been increasingly used in the abdomen, and findings of DWI of different diseases (malignant or inflammatory processes) have been reported (8–10). To our knowledge, some reports have been published in the literature for detection of acute
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Table 1 Demographics and Clinical Features Parameter
Patients (n)
Age (mean) (years) Body mass index (mean) (kg/m2) Sex (M/F) Leukocyte (mean) (x103/mm3) Symptoms Abdominal pain located on RLQ Epigastric pain Diffuse abdominal pain Fever Vomitting Decreased appetite Physical examination RLQ tenderness RLQ guarding RLQ rebound Decreased bowel sound
7 (range: 0–14) 21 (range: 14–30) 27/18 13 (range: 6–20) 26 9 10 18 23 27 38 22 28 19
RLQ ¼ right lower quadrant.
appendicitis in adults with DW MR imaging (11–13). The aim of our study was to determine the accuracy of DWI for the diagnosis of acute appendicitis in children when added and compared with conventional MRI. We hypothesize that DWI will increase the sensitivity/accuracy for imaging diagnosis of acute appendicitis in children compared with conventional MRI alone.
MATERIALS AND METHODS Patients A total of 47 consecutive patients (mean age, 7; range, 0–14 years; 19 girls, 28 boys) with a clinical diagnosis of acute appendicitis and patients with suspected
acute appendicitis or appendix cannot be visualized on US were enrolled in this prospective study during a period of 4 months. The medical ethics committee of our hospital approved the study, and written consent of the parents was obtained before MRI examination. Two patients with claustrophobia were excluded. Ultrasonography was performed to 31 patients. A total of 45 patients had undergone MR imaging. The time range between the ultrasonography and MR imaging was 6–36 h. Thirty-nine of them were operated for acute appendicitis with a mean interval between surgery and MR imaging of 8 h. The remaining six of the patients did not undergo surgery after MR imaging. They were followed clinically over a period of 2 weeks to 2 months. Demographics and clinical features of patients are shown in Table 1. The study population was shown in Figure 1.
Imaging MRI MRI was performed with a 1.5 Tesla (T) body MRI (Magnetom Avanto, Siemens Healthcare) using an 18channel phased-array body coil. Before DWI, the subjects underwent a free-breathing axial and coronal turbo spin-echo T1-weighted sequence (repetition time [TR], 536 ms; echo time [TE], 11 ms; flip angle [FA], 150 ), axial and coronal fat-saturated turbo spin-echo T2-weighted sequence (TR, 5030 ms; TE, 101 ms; FA, 150 ), and an axial diffusion-weighted single-shot spin-echo echoplanar sequence with chemical shift-selective fat-suppression technique (TR/TE, 4900/93); matrix, 192 192; slice numbers, 30; slice thickness, 6 mm; interslice gap, 35%; field of view (FOV), 45 cm; averages, 5; acquisition time, approximately 3 min; PAT factor, 2; PAT mode,
Figure 1. Diagram demonstrating the patients and results. DWI ¼ diffusion-weighted imaging.
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Figure 2. An 11-year-old boy with a normal appendix. a: Axial TSE T2-weighted image showing the appendix. Arrow: appendix. b,c: Diffusion-weighted MR image of the appendix with b value of 400 s/mm2 and 800 s/mm2 showing hypointensity of the appendix. Arrow: appendix. d: ADC image showing hyperintensity of the appendix. ROI was placed on the appendix. ADC was 2.08 103 mm2/s. Arrow: appendix
parallel imaging with modified sensitivity encoding (mSENSE). Diffusion-weighted imaging was performed with b factors of 50, 400, and 800 s/mm2. All slices were acquired from diaphragm to the bottom of the pelvis. Oral and intravenous contrast material was not used. Twenty-six of the patients were sedated and the others did not need sedation for MRI. Imaging Analysis Two radiologists with 10 and 6 years of experience with abdominal MRI reviewed the MR examinations with consensus in an independent workstation (Leonardo console, software version 2.0; Siemens). First, the DW images, including the images with b values of 800 s/mm2 and ADC map were reviewed alone, followed by the conventional MR images, and finally the combined DW images and conventional MR images were reviewed together. This order of image review was kept constant to avoid any recall bias for the DW images, which were always reviewed first. The criteria for the diagnosis of acute appendicitis on MR imaging were thickening of the appendix (>6 mm in outer diameter), intraluminal fluid, and inflammation of the periappendiceal tissue, periappendiceal fluid collections, and markedly hyperintensity on DWI, hypointensity on ADC maps. ADC values were measured using three centrally placed regions of interest, (ROI)
the average value of the three ROIs was the accepted measurement. After a blinded review of the MR examinations, a comparison of the findings of DWI, conventional MRI, and combined DWI and conventional MRI was made with the reference standard was surgery. Statistical Analysis We used a McNemar’s test to analyze the diagnosis of acute appendicitis in children for DWI, conventional MRI, and combined DWI and conventional MRI. In all cases, a two tailed P value was determined, and the null hypothesis was rejected at P < 0.05.
RESULTS The study population and results were shown in Figure 1. Ultrasonography was performed in 31 patients. In 3 patients, ultrasonography findings were normal; in 13 patients, the appendix could not be visualized and the other patients suspected of acute appendicitis on US. Of the 45 patients who had undergone MR imaging with clinically suspected acute appendicitis and suspected acute appendicitis or appendix cannot be visualized on US, 39 patients (86%) were operated on. The remaining six patients, who had clinically
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Figure 3. An 11-year-old girl with acute appendicitis and fluid collection. a: Axial TSE T2-weighted image showing the appendix. Arrow: appendix, f: fluid. b,c: Diffusion-weighted MR image of the appendix with b value of 400 s/mm2 and 800 s/mm2 showing marked hyperintensity. Arrow: appendix; f: fluid. d: ADC image showing hypointensity of the appendix (marked restricted diffusion). ROI was placed on the appendix. ADC was 1.12 103 mm2/s. Arrow: appendix, f: fluid.
suspicious findings for acute appendicitis, were not referred for surgery. They were followed clinically over a period of 2 weeks to 2 months. Findings from followup examinations were unremarkable. In these patients, all imaging modalities showed negative findings for acute appendicitis. Histopathology revealed acute appendicitis in 36 of the operated patients (92%). Four patients had perforated appendicitis in surgery. Three patients had normal appendix in surgery. The operative results of them were the diagnoses of ovarian cyst rupture, Crohn’s disease and Meckel diverticulitis. There was apparently diffusion restriction in the periumblical area at the right lower quadrant in the patient with Meckel’s diverticulitis (1.07 103 mm2/s). In the other two patients, there was no any area showing diffusion restriction (mean ADC value of the appendix ¼ 2.17 6 0.11 103 mm2/s) (Fig. 2). DWI revealed the diagnosis of acute appendicitis in 28 patients (72%) (mean ADC value ¼ 1.12 6 0.17 103 mm2/s) (Figs. 3 and 4). In eight patients with appendicitis at surgery, DWI was negative for acute appendicitis. Three of them were negative for acute appendicitis also by using combined DWI and conventional MRI. In one of these patients, the appendix
could not be demonstrated on MRI but at surgery the appendix, which was located between the urinary bladder and anterior abdominal wall, was perforated. In the other three patients the greatest diameter of appendix was less than 5 mm. In the three patients who were negative for acute appendicitis on only DWI, there was appendicolith and wall thickening of the appendix without periappendiceal fluid or inflammation. In the remaining one patient, the diagnosis was only mesenteric lymphadenitis on DW MRI. Table 2 shows the results of imaging modalities in the diagnosis of acute appendicitis by observers’ consensus. The combination of DWI and conventional MRI was the most sensitive and the most accurate method, depicting 33 cases of acute appendicitis, with corresponding sensitivity and accuracy of 0.92 (P < 0.05). Using DWI alone, observers depicted and localized 28 cases of acute appendicitis (sensitivity: 0.78; and accuracy: 0.77), whereas conventional MRI depicted and localized 29 cases of acute appendicitis (sensitivity: 0.81; and accuracy: 0.82). A case that was misidentified as acute appendicitis (false positive) in DWI was a case of inflamed Meckel’s diverticulum, which was found on surgery.
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Figure 4. An 8-year-old boy with acute appendicitis. a: Axial TSE T2-weighted image showing the appendix (arrow). b,c: Diffusion-weighted MR image of the appendix (arrow) with b value of 400 s/mm2 and 800 s/mm2 showing marked hyperintensity. d: ADC image showing hypointensity of the appendix (marked restricted diffusion). ROI was placed on the appendix (arrow). ADC was 0.97 103 mm2/s.
The McNemar’s Test of Correlated Proportions The combination of DWI and conventional MRI was most sensitive and accurate for acute appendicitis compared with DWI alone (P < 0.05) and conventional MRI alone (P < 0.05) for observers’ consensus. There was no significant difference DWI and conventional MRI (P > 0.05).
DISCUSSION Acute appendicitis is the most common cause of abdominal surgical emergency in children. Although physical examination, laboratory tests, and patient’s history improve the diagnosis, the negative laparotomy
rate is high especially in female patients (14). Further evaluation with radiological techniques like ultrasonography, computed tomography, and MRI is required for minimizing negative laparotomy rates, delayed surgery, and probable complications of perforation. Ultrasonography is an easily available and performed technique in the diagnosis of acute appendicitis with a lack of ionizing radiation. Sonographer-dependency, acute appendicitis with retrocecal location, and obesity are the disadvantages of this method. In these cases, CT is recommended with a sensitivity and specifity of more than 90% (14–17). However, ionizing radiation and the use of iodinated contrast media are disadvantages, and CT is not preferred especially in pregnant women and children (18).
Table 2 Results of Imaging Modalities in the Diagnosis of Acute Appendicitis by the Consensus of Two Observers According to the Histopathological Findings Type of imaging
TP
FN
TN
FP
Sensitivity
Specificity
Accuracy
DWI Conventional MRI Combined MRI
28 29 33
8 7 3
2 3 3
1 0 0
0,78 0,81 0,92
0,67 1,0 1,0
0,77 0,82 0,92
TP ¼ true positive; FN ¼ false negative; TN ¼ true negative; FP ¼ false positive.
DW-MRI in Acute Appendicitis in Children
MRI has become a widely used method with an avoidance of ionizing radiation especially in children and females. It has some disadvantages like long examination time, high cost, and difficulty in claustrophobic patients. Incesu et al. found sensitivity and accuracy of MR imaging in the diagnosis of acute appendicitis to be 97% and 95%, respectively (19). However, in this study fat-suppressed and gadoliniumenhanced MR imaging is recommended. Another study showed that unenhanced turbo spin echo and fatsuppressed images provide accurate diagnosis of acute appendicitis (20). Sensitivity and accuracy of MR imaging in the above-mentioned studies are higher than the present study which might be elucidated with gadolinium use and age of study population. Diffusion-weighted MR imaging is well-established in the setting of acute cerebral infarct and has been more recently shown to help some abdominal diseases. It has been used in abdominal and pelvic oncologic MRI and in inflammatory diseases, such as acute-chronic pancreatitis, renal infections, hepatitis, and liver fibrosis and inflammatory bowel disease (21). This method uses pulse sequences and techniques that are sensitive to very small-scale motion of water protons at the microscopic level (6,7). Inci et al evaluated the utility of DW MRI in the diagnosis of acute appendicitis in adults (11). In this study, the sensitivity and specificity of DW MR imaging for diagnosis of acute appendicitis were found to be 98.7% and 100%, respectively. In our study, we compared the performance of DWI and combined imaging in the evaluation of acute appendicitis in children. For observers’ consensus, the sensitivity was 78% and accuracy was 77%, by using DWI alone. The sensitivity was 81% and accuracy was 82%, by using conventional MRI alone. When DW images were added to conventional MRI sequences, both the sensitivity and accuracy increased (sensitivity: 0.92 and accuracy: 0.92). Relatively poor spatial resolution and increased anatomic distortion of DWI especially in small size of pediatric patients and small number of patients may explain the difference between values of these two studies. They found mean ADC value of inflamed appendix as 1.22 6 0.18 103 mm2/s and 2.02 6 0.19 103 mm2/s of normal appendix similar to ours. Combined DWI and conventional MRI missed only three patients which were surgery proven acute appendicitis. The greatest diameter of the appendix in the two patients was less than 5 mm. The diagnosis of the other one was perforated appendicitis localized between urinary bladder and anterior abdominal wall. Furthermore, two patients were interpreted as not to have appendicitis in imaging sessions but diagnosed as ovarian cyst rupture and Crohn’s disease in surgery. There was one false positive result with DWI. This patient had an inflamed Meckel’s diverticulum found on surgery. In another study, the effectiveness of DW-MRI and ADC values in the diagnosis of acute appendicitis and differentiation of perforated and nonperforated appendicitis cases, with histopathological correlation were evaluated (12). In that study, the sensitivity, specificity, positive predictive value, negative predictive value,
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and accuracy rate of DW-MRI in the diagnosis of acute appendicitis were 97.5%, 100%, 97.5%, 100%, and 98.1%, respectively. The lower results of our study may be explained by the pediatric age group. They found mean ADC value in patients with acute appendicitis (1.01 6 0.26 103 mm2/s) similar with us. Our study has some limitations. One of them is the relatively small number of patients. Larger groups are needed for the evaluation of acute appendicitis with MRI. Second, there was a lack of intravenous and enteric contrast material, which plays an important role in detecting wall enhancement of inflamed appendix and intestine. Third, not only inflammatory diseases but the various other pathologies of this region should be studied with larger groups. Fourth, most of US examinations were done at outside of our center, thus we did not take into account US findings in this study. The inevitable waiting time for MRI—which had not led to any ascribable complications such as perforation or aggravated pain on follow-up in our study— besides requiring skill to assess and not availability in all centers are disadvantages of MRI. In conclusion, diffusion-weighted MR imaging technique is noninvasive, does not require ionizing radiation or injection of contrast material, and can be easily added to an MR examination protocol because it requires only a short time for the examination. This study showed that if DWI is added to the conventional MR imaging, diagnostic accuracy of the imaging method increases for the depiction of acute appendicitis with MRI in pediatric patients with clinical suspicion. Accordingly, diffusion-weighted MR imaging significantly improves the diagnosis of acute appendicitis in our population of children. ACKNOWLEDGMENTS This article was presented as an oral presentation at the ECR 2012 European Congress of Radiology, March 1–5, 2012, in Vienna, Austria. REFERENCES 1. Dunn JCY, Grosfeld JL. Appendicitis pediatric surgery, 6th edition. Chapter 98. Philadelphia, PA: Mosby; 2006. p 1501. 2. Neuspiel DR, Kuller LH. Fatalities from undetected appendicitis in early childhood. Clin Pediatr 1987;26:573–575. 3. Wilson EB, Cole JC, Nipper ML, et al. Computed tomography and ultrasonography in the diagnosis of appendicitis: when are they indicated? Arch Surg 2001;136:670–675. 4. Rao PM, Boland GW. Imaging of acute right lower abdominal quadrant pain. Clin Radiol 1998;53:639–649. 5. Vandecaveye V, De Keyzer F, Vander Poorten V, et al. Evaluation of the larynx for tumour recurrence by diffusion weighted MRI after radiotherapy: initial experience in four cases. Br J Radiol 2006;79:681–687. 6. Le Bihan D, Turner R, Douek P, Patronas N. Diffusion MR imaging: clinical applications. AJR Am J Roentgenol 1992;159:591–599. 7. Le Bihan D. Diffusion, perfusion and functional magnetic resonance imaging. J Mal Vasc 1995;20:203–214. 8. Koh DM, Collins DJ. Diffusion-weighted MRI in the body: applications and challenges in oncology. AJR Am J Roentgenol 2007; 188:1622–1635. 9. Yoshikawa T, Kawamitsu H, Mitchell DG, et al. ADC measurement of abdominal organs and lesions using parallel imaging technique. AJR Am J Roentgenol 2006;187:1521–1530.
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