Does diffusion-weighted magnetic resonance imaging have a place in the differential diagnosis of brucella sacroiliitis and seronegative spondyloarthropathy?

Abstract

Background

The aim of this study is to investigate the role of diffusion-weighted imaging (DWI) in the differential diagnosis of sacroiliitis.

Purpose

To compare the sacroiliac magnetic resonance imaging (MRI) examinations of patients with suspected active sacroiliitis with patients with acute SpA MR findings and the DWI examinations of patients with acute brucella sacroiliitis, and thereby determine whether DWI can contribute to the differential diagnosis.

Material and Methods

A total of 84 patients were included in the study and were separated into three groups: group 1 (13 women, 6 men) comprised cases with brucella positive for sacroiliitis; group 2 (17 women, 19 men) comprised cases negative for brucella but with sacroiliitis; and group 3 (16 women, 13 men) comprised cases negative for brucella and sacroiliitis.

Results

The mean bone marrow apparent diffusion coefficient (ADC) values independently of edema were determined as 0.71 × 10⁻³ in sacroiliitis and brucella-positive patients, as 0.53 × 10⁻³ in brucella-negative and sacroiliitis-positive patients, and as 0.43 × 10⁻³ in the control group of brucella-negative sacroiliitis-negative patients. In the ADC measurements taken from areas of evident edema in patients with sacroiliitis, the mean values were 0.13 × 10⁻³ in the brucella-positive group and 0.12 × 10⁻³ in the brucella-negative group.

Conclusion

By adding DWI, which is a rapid MR sequence, to sacroiliac joint MR examination, normal bone marrow and bone marrow with sacroiliitis can be objectively differentiated with ADC measurements in addition to visual evaluation.

Keywords

Sacroiliitis brucella diffusion-weighted imaging

Introduction

Sacroiliitis, a painful condition of the sacroiliac joint with unilateral or bilateral inflammation, may have infectious or non-infectious causes. One of the infectious causes is brucellosis, which is a zoonosis endemic to some regions such as Mediterranean and Middle Eastern countries and southern and south-eastern regions of Turkey. Brucellosis is a systemic disease that can emerge with different clinical findings and symptoms (1,2). Spread of the disease is generally directly from infected animals or indirectly from the consumption of dairy products such as unpasteurized milk and cheese (3). There is musculoskeletal involvement in 10%–85% of brucellosis cases (4 –6) and sacroiliitis is one of the most frequently seen osteoarticular involvements (5).

Brucellosis usually starts in an acute form with symptoms such as fever, listlessness, joint pain, night sweats, lymphadenopathy, hepatomegaly, and splenomegaly (7 –9). Although rare, it can also be insidious, mimicking rheumatismal diseases and psychosomatic disorders (4,10). In patients with acute lower back pain and no evident findings of infection who do not respond sufficiently to analgesic treatment, sacroiliitis should be considered in the differential diagnosis and the patient should be evaluated in respect of brucellosis (11).

Non-infectious sacroiliitis generally emerges as the first finding of axial spondyloarthritis (SpA) (12,13). SpA is a heterogenous group of chronic inflammatory diseases, including primarily ankylosing spondylitis, psoriatic arthritis, enteropathic arthritis, reactive arthritis, and undifferentiated spondyloarthritis (13,14). Sacroiliitis is one part of the diagnostic criteria of SpA. Of the imaging techniques available, conventional radiography cannot contribute to diagnosis in the early period but magnetic resonance imaging (MRI) allows early diagnosis in the acute/active period (15 –21).

According to the Assessment in SpondyloArthritis International Society (ASAS) criteria for axial SpA, the presence of periarticular or subchondral bone marrow edema (one lesion in at least two sections or more than one lesion in one section) is the basis for a diagnosis of active sacroiliitis with MRI (15). Synovitis, capsulitis, or enthesitis is not sufficient to determine active sacroiliitis.

Diffusion-weighted imaging (DWI) is based on the random diffusion of water molecules in cellular and extracellular tissues and provides both quantitative and qualitative functional information (22–24). The apparent diffusion coefficient (ADC) is a quantitative parameter calculated from DWI, which is the net diffusion of water molecules, reflecting the effects of water diffusion and capillary diffusion in the extravascular extracellular space. DWI has been proven to be an effective diagnostic method evaluating the change in the ratio of intracellular water (with high DWI signal) to extracellular water (with low DWI signal) in the evaluation of active inflammation (25).

In ankylosing spondylitis and seronegative spondyloarthropathies, sacroiliac joint involvement is generally bilateral and symmetric (26). However, there is no specific finding on conventional MR examination for absolute differentiation between seronegative SpA and infectious sacroiliitis, and clinical and laboratory findings may not always be helpful in the differential diagnosis. Differentiation of infectious and seronegtive SpA sacroiliitis is extremely important as the treatments are different (27,28).

The aim of the present study was to compare the sacroiliac MR examinations of patients with suspected active sacroiliitis with patients with acute SpA MR findings and the DWI examinations of patients with acute brucella sacroiliitis, and thereby determine whether or not DWI can contribute to the differential diagnosis.

Material and Methods

Approval for this retrospective study was granted by the Ethics Committee (decision no: HRU/20.06.08). From the radiology clinic records, a retrospective evaluation was made by one specialist radiologists and a physical medicine rehabilitation specialist of patients applied with MR examination of the sacroiliac joint between January 2014 and May 2019. A total of 84 patients were included in the study and were separated into three groups: group 1 (n = 19; 13 women, 6 men) comprised cases with brucella-positive sacroiliitis; group 2 (n = 36; 17 women, 19 men) comprised cases negative for brucella but with sacroiliitis; and group 3 (n = 29; 16 women, 13 men) comprised cases negative for brucella and sacroiliitis. Written informed consent was not obtained from all the participants because of the retrospective nature of the study.

The patients included in the study were patients diagnosed with brucella sacroiliitis and those who were brucella-negative with sacroiliac joint involvement from seronegative arthropathies (ankylosing spondylitis) or with no sacroiliac joint involvement who had sacroiliac joint MR examination because of lower back and hip pain. All the MR examinations were made using a 3-T MR machine (Magnetom Skyra, Siemens) with an 18-channel body coil. In addition to routine contrast MRI of the sacroiliac joint, diffusion MRI with b 1000 value and ADC (TR = 6000 ms, TE = 89 ms, number of excitations = 2, flip angle = 90°) was taken in the axial plane.

Diagnosis of axial SpA was made according to the ASAS criteria. As the region where the study was conducted is an endemic region for brucella, patients with positive laboratory findings for brucella (for scanning, the Rose Bengal Lam agglutination test was used; for diagnosis, the brucella Coombs Wright test was used) and clinical and examination findings of sacroiliitis together with positive MR findings were accepted as brucella sacroiliitis. Patients with no diagnosis of brucella, who could not be diagnosed with axial spondyloarthropathy according to the ASAS criteria, and who could not be diagnosed radiologically with sacroiliitis were included as the control group.

After evaluation of the coronal, axial, and contrast MR images, each sacroiliac joint was separated into four quadrants using a comprehensive global scoring system. From the total eight regions of left and right, quantitative data were obtained by taking ADC measurements from the subchondral regions where the signal increase was most intense in the active early sacroiliitis areas. The measurements in group 3 were taken from subchondral areas in the eight different regions. The region of interest of the measurement was 25 mm² and the measurements were taken from areas other than blood vessels, sclerosis areas, or cystic areas. In addition, by taking ADC measurements from regions with diffusion abnormality in patients determined with brucella sacroiliitis and from patients without brucella with seronegative spondyloarthropathy sacroiliitis, these two parameters were statistically compared with each other.

Data obtained in the study were analyzed statistically using IBM SPSS vn 20 software. The results were stated as mean ± SD, median, minimum, maximum values, number (n), and percentage (%). Conformity of continuous variables to normal distribution was assessed with the Shapiro–Wilk test. In the comparison of more than two independent groups of continuous variables conforming to normal distribution, the ANOVA test was applied, and the Kruskal–Wallis test was used when normal distribution was not shown. After the ANOVA test, post-hoc tests were applied as the Tukey test when there was homogeneity of variances and the Tamhane T2 test was used when variances were not homogenous. After the Kruskal–Wallis test, the Kruskal–Wallis one-way ANOVA (k samples) test was used as the post-hoc test. In comparisons between categorical variables greater than 2 × 2, the Pearson Chi-square test was used when the expected value was > 5, and the Fisher–Freeman–Halton test when the expected value was < 5. When only areas of edema were examined, the ADC measurements taken from regions with diffusion abnormality in patients determined with brucella sacroiliitis and from patients without brucella with seronegative spondyloarthropathy sacroiliitis were compared with the Student’s t-test according to the results of the Shapiro–Wilk test for normal distribution. A value of P < 0.05 was accepted as statistically significant.

Results

Evaluation was made of 19 patients (13 women, 6 men) with brucella-positive acute sacroiliitis, 36 patients (17 women, 19 men) who were negative for brucella but had acute sacroiliitis, and 29 patients (16 women, 13 men) who were negative for brucella and had no clinical, laboratory, or MR findings of sacroiliitis. The mean age of all the groups was 30.17 ± 12.62 years. No statistically significant difference was determined between the groups in respect of age or gender (P > 0.05). Patients with findings of sclerosis or chronic sacroiliitis on MRI, and those with movement artefacts on diffusion examination or images of poor resolution, were excluded from the study.

As a result of the statistical analyses applied to all the regions examined independently of edema, a statistically significant difference was determined between groups 2 and 3 and between groups 1 and 3 in the first region (right iliac bone superior section) (P = 0.011). In the second region (right sacrum superior), a statistically significant difference was determined between groups 1 and 3 (P = 0.013), and in the fourth region (left iliac superior) between groups 1 and 2, and between groups 1 and 3 (P = 0.001). Statistically significant differences were determined between groups 2 and 3 in the fifth region (right iliac inferior) (P = 0.007), between groups 1 and 3 and between groups 2 and 3 in the seventh region (left sacrum inferior) (P = 0.005), and between groups 1 and 3 in the eighth region (left iliac inferior) (Table 1).

Table 1.

Comparison of groups.

	Brucella positive and sacroiliitis positive		Brucella negative and sacroiliitis positive		Brucella and sacroiliitis negative		Chi-squared test	P	Post-hoc test
Tb1	688.89 ± 388.14	709.5 (124.6–1594.63)	673.05 ± 360.57	527.29 (124.64–1775.31)	450.5 ± 183.14	417.13 (181.31–840.9)	8.997	0.011	2–3, 3–1
Tb2	695.22 ± 265.13	714.4 (315.99–1351.9)	643.17 ± 466.39	451.18 (136.29–1820.06)	442.94 ± 202.78	390.2 (139.92–992.82)	8.701	0.013	1–3
Tb3	612.54 ± 266.21	581.68 (133.3–1162.4)	534.88 ± 329.44	412.26 (133.8–1454.03)	419.72 ± 133.01	477.61 (209.01–681.28)	5.768	0.056
Tb4	712.26 ± 248.05	677.9 (180.26–1133.5)	537.56 ± 293.86	487.95 (106.58–1334)	437.31 ± 163.82	412.28 (126.91–947.76)	14.112	0.001	1–2, 1–3
Tb5	619.1 ± 274.59	625.67 (153.19–1171.07)	780.57 ± 421.4	662.27 (177.66–1679.16)	473.66 ± 142.89	495.55 (148.39–730.68)	10.006	0.007	2–2
Tb6	530.29 ± 194.35	544.3 (176–898)	563.51 ± 334.57	467.16 (82.4–1477.66)	399.58 ± 170.53	354.66 (149.67–713.85)	5.893	0.053
Tb7	629.85 ± 314.3	584.29 (188.91–1684.62)	643.89 ± 363.4	572.42 (138.2–1464.57)	413.21 ± 162.99	425.2 (105.07–749.84)	10.427	0.005	1–3, 2–3
Tb8	681.6 ± 340.63	663 (245.21–1587.36)	676.69 ± 393.68	571.21 (53.58–1546.06)	456.23 ± 170.6	418.72 (197.59–983.84)	7.091	0.029	1–3

Values are given as mean ± SD or median (range).Tb1, right iliac bone süperior section; Tb2, right sacral bone süperior section; Tb3, left sacral bone süperior section; Tb4, left iliac bone süperior section; Tb5, right iliac bone inferior section; Tb6, right sacral bone inferior section; Tb7, left sacral bone inferior section; Tb8, left iliac bone inferior section.

The mean bone marrow ADC values independently of edema were determined as 0.71 × 10⁻³ ± 0.24 × 10⁻³ in sacroiliitis and brucella-positive patients (Fig. 1), as 0.53 × 10⁻³ ± 0.29 × 10⁻³ in brucella-negative and sacroiliitis-positive patients (Fig. 2) and as 0.43 × 10⁻³ ± 0.16 × 10⁻³ in the control group of brucella-negative sacroiliitis-negative patients (Fig. 3). In the ADC measurements taken from areas of evident edema in patients with sacroiliitis, the mean values were 0.13 × 10⁻³ ± 0.17 × 10⁻³ in the brucella-positive group and 0.12 × 10⁻³ ± 0.19 × 10⁻³ in the brucella-negative group.

Fig. 1.

Axial FS T2W image (a) and axial ADC weighted MR images (b) show ADC values in sacroiliitis and brucella-positive patients. ADC, apparent diffusion coefficient; FS, fat-saturated; MR, magnetic resonance; T2W, T2-weighted.

Fig. 2.

Axial FS T2W image (a) and axial ADC weighted MR images (b) show ADC values in brucella-negative and sacroiliitis-negative patients. ADC, apparent diffusion coefficient; FS, fat-saturated; MR, magnetic resonance; T2W, T2-weighted.

Fig. 3.

Axial FS T2W image (a) and axial ADC weighted MR images (b) show ADC values in brucella-negative and sacroiliitis-positive patients. ADC, apparent diffusion coefficient; FS, fat-saturated; MR, magnetic resonance; T2W, T2-weighted.

The ADC values were determined to be lower in the patients without sacroiliitis compared to those with sacroiliitis. Higher values were measured in all the regions independently of edema in patients with brucella sacroiliitis compared to patients with SpA sacroiliitis only without brucella. No statistically significant difference was determined in the ADC measurements taken from regions with diffusion abnormality in patients determined with brucella sacroiliitis and from patients without brucella with seronegative spondyloarthropathy sacroiliitis (P = 0.221).

Discussion

The differential diagnosis of infectious and inflammatory sacroiliitis is extremely important as the treatments are very different from each other (29,30). Therefore, early diagnoss of sacroiliitis is helpful in preventing complications (31). In the present study, it was examined whether ADC measurements on DWI in addition to clinical and laboratory findings could contribute to the differential diagnosis of infectious sacroiliitis secondary to brucella infection and inflammatory sacroiliitis. The aim of this was to reveal whether DWI alone could contribute to the differential diagnosis of infectious sacroiliitis and inflammatory sacroiliitis. To the best of our knowledge, this is the first study to have used DWI in addition to conventional MRI in the differentiation of inflammatory and infectious sacroiliitis.

In a study by Sahin et al. (32), the mean ADC value in normal bone marrow in the control group was measured as 0.56 × 10⁻³ mm²/sn. In the literature, normal vertebral bone marrow ADC values have been reported in the range of 0.15–0.67 × 10⁻³ mm²/sn (17,18). In the present study, we found the mean ADC values of bone marrow adjacent to sacroiliac joint in the control group to be in the range of 0.10–0.98 × 10⁻³ mm²/sn. In the group with brucella sacroiliitis, ADC values was measured in the range of 0.12–0.16 × 10⁻³ mm²/sn. ADC values in the hyperintense regions where there is bone marrow edema in patients with axial SpA patients were measured as 1.31 × 10⁻³ mm²/sn, which was much higher than the measurements of bone marrow which appeared normal in patients with axial SpA evaluated as the control group (17,18). In the current study, the ADC values of bone marrow independent of edema were determined as 0.71 × 10⁻³ in sacroiliitis and brucella-positive patients, as 0.53 × 10⁻³ in brucella-negative sacroiliitis-positive patients, and as 0.43 × 10⁻³ in brucella-negative sacroiliitis-negative patients evaluated as the control group.

In the study by Sahin et al. (32), the use of DWI sequences without the need for contrast was evaluated as an alternative to conventional MRI sequences and contrast imaging in sacroiliitis diagnosis, and it was determined that DWI examination in addition to fat-suppressed T2 or STIR MR sequences could be complementary in the correct diagnosis and follow-up of inflammatory sacroiliitis. Bozgeyik et al. (17) determined higher ADC values in early sacroiliitis than in mechanical lower back pain and suggested that DWI could be used in the early diagnosis and follow-up of acute inflammatory lesions of the sacroiliac joint.

In a study by Gezmis et al. (18), higher ADC values were determined in normal appearance subchondral areas adjacent to the sacroiliac joint of patients with axial SpA than in the control group. This was thought to be associated with the increased movement of water molecules in bone marrow edema. However, higher values were determined in the ADC measurements taken from regions of normal appearance without any signal change. Therefore, it was recommended that before diffusion examination, evaluation should be made visually then quantitative ADC measurements should be taken. Similarly, in the current study, higher values were measured in patients with sacroiliitis in the measurements taken independently of edema.

In contrast, Sahin et al. (32) found that the mean ADC values in bone marrow of normal appearance adjacent to the sacroiliac joint were not very different to those of the control group, which was similar to the findings of Sanal et al. (19). In another study by Gasperic et al. (25), both DWI and dynamic contrast MRI were found to be effective in the quantification of inflammatory changes in the treatment of ankylosing spondylitis.

In the present study, the normal subchondral bone marrow ADC values were measured at a significantly lower level than in both brucella sacroiliitis and in axial SpA sacroiliitis. Thus, by taking a diffusion MR sequence, which is a rapid sequence, in cases with general condition impairment, the presence of sacroiliitis and etiology can be predicted. A statistically significant difference was determined in respect of ADC values between region 4 (left iliac superior) in group 1, the brucella sacroiliitis group, and group 2, the patients who were brucella-negative but with sacroiliitis.

However, no statistically significant difference was determined between the ADC measurements taken from regions with diffusion abnormality in patients determined with brucella sacroiliitis and from patients without brucella with seronegative spondyloarthropathy sacroiliitis. Therefore, the hypothesis was not supported that DWI could be of guidance in the differentiation of these two forms of sacroiliitis.

There were some limitations to this study, primarily that it was retrospective in design, the number of patients was relatively low, and there was no pathology confirmation.

In conclusion, by adding DWI, which is a rapid MR sequence, to sacroiliac joint MR examination, normal bone marrow and bone marrow with sacroiliitis can be objectively differentiated with ADC measurements in addition to visual evaluation. However, it could not be determined with ADC measurements whether the subchondral signal increases were associated with infectious or non-infectious pathologies. Therefore, there is a need for further extensive studies on this subject.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Sunay Sibel Karayol

References

Buzgan

Karahocagil

Irmak

, et al. Clinical manifestations and complications in 1028 cases of brucellosis: a retrospective evaluation and review of the literature. Int J Infect Dis 2010; 14:469–478.

Saçar

Hırçın Cenger

, et al.

Otuz bruselloz olgusunun klinik değerlendirilmesi. İnfeksiyon Dergisi

2008; 22:11–14.

Yüce

Alp-Çavuş

Türkiye’de bruselloz: genel bakış.

Klimik Derg 2006; 19:87–97.

Tezer

Kara

Devrim

, et al. Brusella sakroilleitti: Bir vaka takdimi. Çocuk Sağlığı ve Hastalıkları Dergisi 2006; 49:225–228.

Arkun

Mete

BD.

Musculoskeletal brucellosis. Semin Musculoskelet Radiol 2011; 15:470–479.

Geyik

Gur

Nas

, et al. Musculoskeletal involvement of brucellosis in different age groups: A study of 195 cases. Swiss Med Wkly 2002; 132:98–105.

Corbel

MJ.

Brucellosis: an overview. Emerg Infect Dis 1997; 3:213–221.

Memish

Balkhy

HH.

Brucellosis and international travel. J Travel Med 2004; 11:49–55.

Pappas

Akritidis

Bosilkovski

, , et al. Brucellosis. N Engl J Med 2005; 352:2325–2336.

10.

Young

ES.

An overview of human brucellosis. Clin Infect Dis 1995; 21:283.

11.

Bal

Ünlüsoy

Ünlü

, et al. Akut bel ağrısıyla başvuran bir hastada brusella sakroileiti. Nobel Med 2007; 3:23–26.

12.

Braun

Sieper

The sacroiliac joint in the spondyloarthropathies. Curr Opin Rheumatol 1996; 8:275–287.

13.

Navallas

Ares

Beltrán

, et al. Sacroiliitis associated with axial spondyloarthropathy: new concepts and latest trends. RadioGraphics 2013; 33:933–956.

14.

Rudwaleit

van der Heijde

Khan

, et al. How to diagnose axial spondyloarthritis early. Ann Rheum Dis 2004; 63:535–543.

15.

Sieper

Rudwaleit

Baraliakos

, et al. The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis. Ann Rheum Dis 2009; 68 (Suppl. 2):1–44.

16.

Hermann

Bollow

Magnetic resonance imaging of sacroiliitis in patients with spondyloarthritis: correlation with anatomy and histology. Rofo 2014; 186:230–237.

17.

Bozgeyik

Ozgocmen

Kocakoc

Role of diffusion-weighted MRI in the detection of early active sacroiliitis. AJR Am J Roentgenol 2008; 191:980–986.

18.

Gezmis

Donmez

Agildere

Diagnosis of early sacroiliitis in seronegative spondyloarthropathies by DWI and correlation of clinical and laboratory findings with ADC values. Eur J Radiol 2013; 82:2316–2321.

19.

Sanal

Yilmaz

Simsek

, et al. Apparent diffusion coefficients of sacroiliitis in patients with established ankylosing spondylitis. Clin Imaging 2013; 37:734–739.

20.

Boy

Kayhan

Karakas

, et al. The role of multi-parametric MR imaging in the detection of early inflammatory sacroiliitis according to ASAS criteria. Eur J Radiol 2014; 83:989–996.

21.

Althoff

Feist

Burova

, et al. Magnetic resonance imaging of active sacroiliitis: do we really need gadolinium? Eur J Radiol 2009; 71:232–236.