The Spearman's rho correlation analysis exhibited a highly positive correlation between ADC and Fenh values in ilium (P = .000 <.05, r = 0.744; Fig. 1), between ADC and Fenh values in sacrum (P = .000 <.05, r = 0.702; Fig. 2), and between ADC and Senh values in ilium (P = .000 <.05, r = 0.738; Fig. 3). However, a moderate positive correlation was exhibited in ADC and Fenh values in sacrum (P = .000 <.05, r = 0.547; Fig. 4).
The main manifestation of AS was progressive inflammation in the sacroiliac joint and spine little joints, with a possible correlation with heredity and environment but with an unclear pathogenesis.
In the clinical diagnosis and treatment process, imaging is an important method to evaluate the activity in AS and monitor for any changes. In the past, it was generally believed that X-ray film was the first method to evaluate the sacroiliac arthritis of the patients with mandatory spondylitis. However, some studies and clinical practice have found that X-ray is less sensitive to sacroiliac joint lesions, especially when there is no bone change in early AS. In addition, X-ray film can only better show the direction of the same direction of the joint surface and bone space, but not more detailed multi-angle observation of the lesion. Therefore, X-ray plain film for early diagnosis of sacroiliac joint has certain limitations, and its clinical significance is relatively low in the clinic practice.
The advantages of CT include its wide availability, speed of image acquisition, relatively low cost and multi-dimensional reconstruction. However, the main concern of CT is the risk of exposure to ionizing radiation, especially in patients requiring continuous studies to monitor the efficacy of treatments. Comparing with X-ray, CT can not only display the whole structure of sacroiliac joint but also better observe the changes of pathological details, such as bone trabecular changes, subarticular wormlike bone destruction, articular surface roughness, bone cyst lesions, bone hyperplasia, and sclerosis and other changes in bone structure. Compared with MRI, the changes of bone marrow edema, fat deposition cannot be shown on CT, which has some limitations in evaluating the active value of sacroiliac arthritis.
MRI is a non-invasive examination with multi-parameter, multi-plane imaging, which can effectively show fat deposition and so on, articular cartilage signal changes, bone marrow edema. Therefore, MRI has great advantages compared with traditional radiological examination methods (X-ray, CT). In recent years, many studies have shown that MRI has unique advantages in sacroiliac joint lesions, especially in the early sensitivity to inflammation. It was reported that MRI is generally recognized as the most sensitive and specific clinical examination for diagnosing sacroiliac arthritis at the clinical radiology Symposium on sacroiliac arthritis held in Austria in 2003.
Using MRI to diagnose and evaluate active AS has been widely accepted, including different scoring systems and functional MRI methods, such as diffusion-weighted imaging (DWI) and DCE-MRI.[9,10]
DWI and DCE-MRI may be effective methods in quantifying inflammatory changes at involved skeletal sites and useful for assessing treatment efficacy in ankylosing shown by some recent studies.[1,11] However, the ADC value in
DWI is affected by b value l, and semiquantitative parameters derived from the signal intensity–time curve in DCE-MRI could only reflect the characteristics of tissue enhancement. Quantitative permeability parameters were derived using a pharmacokinetic model through analysis of the signal intensity–time curve of the tissues. At present, some experts suggest that DWI and DCE-MRI may not only be effective methods in quantifying inflammatory changes at involved skeletal sites but also useful for assessing treatment.
In this study, we observed the change of water molecule diffusion state by measuring the ADC value, analyzed the changes of blood perfusion states by signal intensity time relation (TIC) curve, Fenh, Senh and peak time Tmax value, and discussed the correlation between ADC value and Fenh and Senh values in sacroiliac joint lesions of AS before and after treatment.
4.1 Imaging features of AS in MRI routine sequences
The T1-weighted images (T1WIs) displayed the structure of the sacroiliac joint cartilage and subchondral region and provided some value in the differentiation of subchondral bone marrow fat deposition. The T2-weighted images (T2WIs) displayed joint effusion and distinguished between articular cartilage and joint effusion effectively through a large signal contrast. STIR sequences exhibited the structure and pathological changes in the sacroiliac joint and effectively identified the abnormal changes in bone marrow edema and fat deposition. The degree of inflammation of AS was analyzed mainly from articular cartilage, bone marrow edema, joint effusion, and fat deposition. An abnormal change in articular cartilage is a reliable sign of early AS, which are manifested mainly as normal signal interruption, disappearance and cartilage surface roughness, and fragmentation on the T1WIs and T2WIs. The abnormal articular cartilage signal exhibited mixed hyperintense and hypointense signal on T1WIs and irregular hyperintense signal onT2WIs. The main manifestations of bone marrow edema exhibited patchy hypointense signal on T1WIs, and hyperintense signal on T2WIs and STIR images. The joint effusion displayed low signal on T1WIs and high signal on T2WIs. The fat deposition displayed hyperintense signal on T1WIs and T2WIs and hypointense signal on STIR sequences. Asymmetric fat deposition in the bone marrow is more valuable in the diagnosis of AS.
4.2 DWI changes in early AS after treatment
Diffusion-weighted MR imaging (DWI) is the only imaging method based on the water molecular detection, in which image contrast is due to the different random motions of water protons in different biological tissue environments. The method has proven to be an effective diagnostic tool whenever a change in the ratio of extracellular water (with low DWI signal) to intracellular water (with high DWI signal) occurs, which may be due to inflammation. Diffusion is thrandom thermal motion of gaseous or liquid molecules and MR imaging can detect signal changes caused bpositional changes of molecules. In biological tissue, Water exchange occurs between intracellular and extracellular compartments and is based on the shape of the extracelular space and tissue cellularity, which affect diffusion. DWI was obtained by applcation of symmetric pairs of equally weighted diffusion sensitizing gradients about the 180refocusing pulse of spin echo T2-weighted sequence. The reduction on diffusion MR imaging can be quantified by calculating the apparent diffusion coeffcient (ADC), which depends largely on the presence obarriers to diffusion within the water micro-environment.
Diffusion sensitive factor (b value) is the diffusion sensitivity coefficient of DWI. It is an index to detect the sensitivity of water molecule free diffusion. The b value is proportional to the sensitivity of water molecule movement and the change of signal and the sensitivity of water molecule movement increases with the increase of the b value. It is the product of the gyromagnetic ratio, the strength of the diffusion-sensitizing gradients, the duration of the gradienpulse and the time interval between gradient pairs.[17–19] The choice of b value is most likely the pivotal issue of diffusion MR imaging. Diffusion-weighted imaging is typically performed with at least 2 b values to allow for the calculation of the ADC value. Previous studies reported that the structure of peri-sacroiliac joint tissue would be better reflected and the clinical observation would be better performed with a best “b value” of 600 s/mm2. For patients with early AS in sacroiliac joints, incrassation of synovial lining cell layer infiltration of inflammatory cells, formation of pannus, and invasion of subarticular sclerotin resulted in bone marrow edema that was reflected in the subsacroiliac joint surface bone marrow area as a spot or patchy diffusion-restricted region (high signal area) on DWI image.
The diffusion coefficient (D) was used to measure the range of free movement of water molecules. However, ADC values were used to quantify the diffusion rate of water molecules because D is easy to be affected by many factors. In the present study, the ADC value of AS lesions increased in the bone marrow edema area. Bozgeyik believed that the presence of bone marrow edema leads to acceleration of the local water molecule movement, strengthening of the free diffusion movement, and increase in the ADC value of the diseased area.
Before clinical treatment, the mean of ADC value of the subarticular surface bone marrow of patients was (5.05 ± 1.10) × 10−4 mm2/s in ilium and (4.63 ± 0.79) × 10−4 mm2/s in sacrum. The mean of ADC value after the clinical intervention treatment group was (4.34 ± 0.55) × 10−4 mm2/s in ilium and (3.96 ± 0.23) × 10−4 mm2/s in sacrum, and both of them were significantly lower than those before treatment (P <.05). Therefore, these data revealed that the degree of infiltration of inflammatory cells, formation of pannus, and formation of bone marrow edema decreased after intervention treatment. Moreover, the region for restricted water diffusion became smaller in the corresponding position, and the signal of the DWI diffusion-restricted region reduced with ADC value lowered compared with that before treatment (Fig. 5). However, the ADC value was still slightly higher than that of the contrast group because of slight or chronic inflammation.
4.3 DCE changes in early AS after treatment
Dynamic contrast enhanced MRI (DCE-MRI) is a method that visualizes the kinetics of body fluids by rapid injection of a bolus of contrast agent and dynamic imaging of the bolus passage in an organ of interest. Tracer kinetic modeling with DCE-MRI and the quantitative evaluation of the kinetic parameters is a particularly active field of research because the superior spatio-temporal resolution of MRI offers possibilities that are not available to nuclear.
DCE-MRI is a method that can indirectly reflect the status of blood perfusion and the degree of vascularization through an intravenous injection of water-soluble contrast agent. The changes in hemodynamics take advantage of semiquantitative or qualitative analysis of multiple variable values. The qualitative analysis was performed based on the morphological changes in the TIC curve, and the semiquantitative analysis was performed based on the multivariate analysis of normal tissue or lesion enhancement mode. Therefore, DCE-MRI can not only evaluate the changes in capillary permeability, microcirculation, and blood flow in the lesion area but also directly reflect the blood perfusion rate of the lesion area. In the present study, DCE-MRI is used mainly to observe the degree of blood vessel and the blood flow perfusion in the articular surface bone marrow of the sacroiliac joint in the before- and after-treatment groups, and also to make an objective and real assessment of inflammatory changes and therapeutic effects of AS. The type of TIC curve of the sacroiliac joint was roughly divided into 3 types based on previous studies:
- as a platform,
- to speed up/slow down, and
- for slow rise/slow down.
In the DCE–MRI follow-up treatment imaging of 48 patients with AS (192 parts), the TIC curve type recorded was as follows: 43.75% (84/192) of type II, 56.25% (108/192) of type III, and type I curve were not seen. The number of type II curve was significantly reduced in the after-treatment group (84 cases) compared with that in the before-treatment group (124 cases). After drawing the TIC curve, the SI0, SImax, and TTP were recorded, and the Fenh and Senh values were calculated. The Fenh, Senh, and TTP values before clinical treatment were as follows: Fenh (113.38 ± 44.71) % in ilium and (83.03 ± 20.39) % in sacrum, Senh (60.94 ± 38.56) % min in ilium and (44.91 ± 15.19) % min in sacrum and TTP (129.52 ± 42.66) s in ilium and (123.44 ± 28.50) s in sacrum. Following treatment, Fenh was (75.90 ± 17.97) % in ilium and (73.28 ± 15.67) % in sacrum, Senh was (33.96 ± 11.36) % min in ilium and (31.92 ± 8.15) % min in sacrum, and TTP was (138.67 ± 26.60) s in ilium and (140.19 ± 19.88) s in sacrum. Analyzing the aforementioned data, the Fenh and Senh values after treatment were found to be significantly lower than those of the before-treatment group. The TTP values were longer than those of the before-treatment group (Fig. 5). Significantly statistical differences were observed for patients between before- and after-treatment groups (P <.05). The results exhibited that in the treatment group, the synovial proliferation pannus of the sacroiliac joint lesion area was reduced and absorbed, with vascular permeability recovering and the inflammatory cell infiltration reducing, and the degree of contrast enhancement weakened.
4.4 “Spearman's rho” correlation analysis of ADC, Fenh, and Senh values
In the present study, the “Spearman's rho” correlation analysis was performed between ADC values and Fenh and Senh values in the sacroiliac joint in the treatment group. The correlation coefficient between ADC and Fenh values of the iliac side was r = 0.744 and that of the sacral side was r = 0.702, which were highly positively correlated. A highly positive correlation existed between ADC and Fenh values of ilium and sacrum, which reflect to some extent that both the ADC and Fenh values rose and fell corresponding to the change in inflammatory activity. From the aforementioned analysis, the present study speculated that the higher the ADC values of the bone marrow zone of the sacroiliac joint, the greater the possibility of the Fenh values of the corresponding site. Similarly, when the degree of Fenh values is higher, the corresponding parts of the ADC values may be higher. The rise and decrease of ADC and Fenh values shift correspondingly with the changes in the inflammatory activity in AS.
Additionally, a significant difference was observed in the ADC and Senh values in the ilium of the sacroiliac joint, and the correlation coefficient were r = 0.738, which was highly positive. However, a moderate positive correlation was observed between ADC and Senh values in the sacrum, and the correlation coefficient was r = 0.547. A highly positive correlation existed between the ADC and Senh values of ilium, and a moderately positive correlation existed between the ADC and Fenh values of ilium, and it is relevant to the sacroiliac joint special physiological anatomy and the pathological basis of AS. The pannus invasion of ilium side was more easily done compared with the sacrum side so that the vascularization, inflammatory cell infiltration of sacroiliac joints under the surface of the bone, and formation of bone marrow edema appeared earlier, resulting in a higher degree of inflammation, stronger contrast enhancement, and shorter TTP. This is the reason for the difference in performance between the ADC and Senh values of the ilium and sacrum side.
5 Limitations or inadequacies
- The sample number of the study is relatively small and very strong regionality.
- All the patients were treated with the combination of Chinese and Western medicine, which the dosage and duration of drugs were not entirely consistent because of difficultly unify the personal specific conditions in all patients, which were its shortages.
- The diagnostic criteria for AS are human factors, which may lead to false positive results.
- The follow-up period was relatively short for 6 months, whether long-term treatment is in line with linear regression trend needs further study with longer follow-up times.
- There was no detailed grouping of gender and not ruled out age the influence of sex and age on bone marrow changes.
- Semi-quantitative analysis can only show a trend of change, but it is more meaningful without quantitative analysis. We plan to study the value of quantitative analysis for AS in the future.
In conclusion, it is sensitive for conventional MRI sequence to check the high inflammation in patients with AS. For early AS, no obvious bone marrow edema exists, or only a small range of bone marrow edema exists, which is displayed using the conventional MRI scan. The DWI and DCE sequence, which can effectively reflect the AS early treatment condition, and could be applied to access AS inflammation activity changes, reflect the curative effect for patients with early AS, and provide reliable radiological evidence for clinical therapeutic efficacy.
Thanks to my teacher's guidance and support. Thanks for the help of my colleagues.
Thanks to clinicians and patients friendly cooperation with us.
Conceptualization: Zhaojuan Shi, Jiankui Han.
Data curation: Jiankui Han, Jian Qin, Yue Zhang.
Formal analysis: Zhaojuan Shi, Jiankui Han, Yue Zhang.
Investigation: Zhaojuan Shi, Jiankui Han, Jian Qin.
Methodology: Zhaojuan Shi, Yue Zhang.
Project administration: Jiankui Han.
Supervision: Jian Qin.
Validation: Zhaojuan Shi.
Visualization: Yue Zhang.
Writing – original draft: Zhaojuan Shi, Jiankui Han.
Writing – review & editing: Jian Qin, Yue Zhang.
. Gaspersic N, Sersa I, Jevtic V, et al. Monitoring ankylosing spondylitis
therapy by dynamic contrast-enhanced
and diffusion-weighted magnetic resonance
imaging. Skeletal Radiol 2008;37:123–31.
. Ji W, Li J, Lin Y, et al. Report of 12 cases of ankylosing spondylitis
patients treated with Tripterygium wilfordii. Clin Rheumatol 2010;29:1067–72.
. Braun J, Zochling J, Baraliakos X, et al. Efficacy of sulfasalazine in patients with inflammatory back pain due to undifferentiated spondyloarthritis and early ankylosing spondylitis
: a multicentre randomised controlled trial. Ann Rheum Dis 2006;65:1147–53.
. Jansen JP, Gaugris S, Choy EH, et al. Cost effectiveness of etoricoxib versus celecoxib and non-selective NSAIDS in the treatment of ankylosing spondylitis
. Pharmacoeconomics 2010;28:323–44.
. Vegvari A, Szabo Z, Szanto S, et al. The genetic background of ankylosing spondylitis
. Joint Bone Spine 2009;76:623–8.
. Pepmueller PH, Moore TL. Juvenile spondyloarthropathies. Curr Opin Rheumatol 2000;12:269–73.
. Razek AA, Tawfik AM, Elsorogy LG, et al. Perfusion CT of head and neck cancer. Eur J Radiol 2014;83:537–44.
. Klauser A, Bollow M, Calin A, et al. Workshop report: clinical diagnosis and imaging of sacroiliitis, Innsbruck, Austria, October 9, 2003. J Rheumatol 2004;31:2041–7.
. Algin O, Gokalp G, Baran B, et al. Evaluation of sacroiliitis: contrast-enhanced MRI with subtraction technique. Skeletal Radiol 2009;38:983–8.
. Althoff CE, Feist E, Burova E, et al. Magnetic resonance
imaging of active sacroiliitis: do we really need gadolinium. Eur J Radiol 2009;71:232–6.
. Bozgeyik Z, Ozgocmen S, Kocakoc E. Role of diffusion-weighted MRI in the detection of early active sacroiliitis. AJR Am J Roentgenol 2008;191:980–6.
. Sourbron SP, Buckley DL. Classic models for dynamic contrast-enhanced
MRI. NMR Biomed 2013;26:1004–27.
. Zhang M, Zhou L, Huang N, et al. Assessment of active and inactive sacroiliitis in patients with ankylosing spondylitis
using quantitative dynamic contrast-enhanced
MRI. J Magn Reson Imaging 2017;46:71–8.
. HQ. S. Early ankylosing spondylitis
sacroiliac joint lesions in MRI [M. S. thesis]. Shandong University. 2007.
. Berman RM, Brown AM, Chang SD, et al. DCE MRI of prostate cancer. Abdom Radiol (NY) 2016;41:844–53.
. Razek AA. Diffusion magnetic resonance
imaging of chest tumors. Cancer Imaging 2012;12:452–63.
. Luna A, Sanchez-Gonzalez J, Caro P. Diffusion-weighted imaging
of the chest. Magn Reson Imaging Clin N Am 2011;19:69–94.
. Luna A, Martín T, González JS. Diffusion-Weighted Imaging
in the Evaluation of Lung, Mediastinum. Springer Berlin Heidelberg: Heart, and Chest Wall; 2012.
. Henzler T, Schmid-Bindert G, Schoenberg SO, et al. Diffusion and perfusion MRI of the lung and mediastinum. Eur J Radiol 2010;76:329–36.
. Qin J, Zhao LP, Zhu JZ, et al. The standard values of normal sacroiliac joint on DWI and DCE MRI secquences. Orthop J Chin 2014.
. Zikic D, Sourbron S, Feng X, et al. Automatic alignment of renal DCE-MRI image series for improvement of quantitative tracer kinetic studies. Proc SPIE Int Soc Optic Eng 1980;167:334–42.
Keywords:Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
ankylosing spondylitis; diffusion-weighted imaging; dynamic contrast-enhanced; magnetic resonance; therapeutic effect