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ORIGINAL ARTICLE
Year : 2022  |  Volume : 35  |  Issue : 4  |  Page : 1890-1896

Role of adding coronal short T1 inversion recovery (STIR) sequence to MRI for evaluation of low back pain


1 Department of Radiodiagnosis, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Radiodiagnosis, Ministry of Health, Menoufia, Egypt

Date of Submission25-Jun-2022
Date of Decision16-Jul-2022
Date of Acceptance17-Jul-2022
Date of Web Publication04-Mar-2023

Correspondence Address:
Mohamed S. A. A. Alhefnawy
Shebin Elkom, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_215_22

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  Abstract 


Background
Short TI inversion recovery (STIR) sequence is one of the inversion recovery (IR) pulse sequences and is the most commonly used. The addition of a coronal STIR sequence is thought to be useful in detection of extraspinal etiologies of sciatica that may be missed on routine imaging protocol.
Objective
To assess the value of adding coronal STIR images to routine MRI protocol of lumbosacral spines aiming to detect extraspinal causes of sciatica.
Patients and methods
This prospective observational study was carried out between December 2019 and June 2020 on 300 patients (169 males, representing 56%, and 131 females, representing 44%). They presented with low back pain and were referred to perform routine lumbosacral spine MRI examination. We added a large field of view coronal STIR sequence to the routine protocol to investigate its capability to detect extraspinal causes of sciatica.
Results
Additional coronal STIR images detected extraspinal abnormalities in 21.3% of the patients, thereby downgraded normal studies from 40.7 to 24.7%. The extraspinal abnormalities included osteoarthritic abnormalities and stress fractures (n = 25; 39.1%), soft tissue abnormalities (n = 2, 4.5%), neurological abnormalities (n = 4, 6.3%), gynecological abnormalities (n = 31, 48.4%), and miscellaneous (n = 4, 6%).
Conclusion
Additional coronal STIR images helped to identify extraspinal abnormalities that were overlooked on routine MRI protocol in patients presenting with sciatica.

Keywords: coronal, extraspinal, MRI, sciatica, short TI inversion recovery


How to cite this article:
Serag DM, Alhefnawy MS, Abdullah MS. Role of adding coronal short T1 inversion recovery (STIR) sequence to MRI for evaluation of low back pain. Menoufia Med J 2022;35:1890-6

How to cite this URL:
Serag DM, Alhefnawy MS, Abdullah MS. Role of adding coronal short T1 inversion recovery (STIR) sequence to MRI for evaluation of low back pain. Menoufia Med J [serial online] 2022 [cited 2024 Mar 29];35:1890-6. Available from: http://www.mmj.eg.net/text.asp?2022/35/4/1890/370980




  Introduction Top


Sciatica is defined as low back pain that radiates to the legs, with or without neurologic deficiency. Patients may present with nonradiating low back pain, buttock pain, thigh or leg pain, and sensory/motor deficits, which are referred to as sciatica-like symptoms [1]. In most cases, sciatica or sciatica-like symptoms is caused by lumbar nerve roots compression secondary to discogenic disease. However, in some cases, such symptoms may result from nerve compression in an extraspinal location where pathologies involving the lumbosacral plexus or sciatic nerve at the pelvis, gluteal region, and upper thigh are suggested to be the causative factor. Such conditions have been reported in literature as 'extraspinal sciatica' [2],[3].

Variable etiologies can be behind extraspinal sciatica: traumatic, infective, neoplastic, vascular, and gynecological, all of which might be easily overlooked on routine MRI protocol. Although MRI is the modality of choice for investigating sciatica, its routine protocol, constituted by sagittal views of the lumbar spine and axial views along the disc planes, does not allow detection of extraspinal causes of sciatica or sciatica-like symptoms [3],[4].

Short TI inversion recovery (STIR) sequence is one of the inversion recovery (IR) pulse sequences and is the most commonly used. With STIR sequences, all tissues of short T1 relaxation times, including fat, are suppressed, whereas tissue with high water content, including most pathologic lesions, are accentuated, yielding a bright signal on a dark background of nullified short-T1 tissue [5]. Adding a STIR sequence in coronal view to cover the bony pelvic girdle and surrounding soft tissues, including the lumbosacral plexus and branches, is thought to be useful in detection of extraspinal etiologies of sciatica and sciatica-like symptoms that may be missed on routine imaging protocol [4],[6],[7].

The aim of our study was to assess the value of adding coronal STIR images to routine MRI protocol of sciatica to detect extraspinal causes of sciatica.


  Patients and methods Top


To elucidate our results, this prospective observational study was carried out between December 2019 and June 2020 on 300 patients (169 males, representing 56%, and 131 females, representing 44%), with a mean age of 47 years, and age range from 20 to 70 years. They were complaining of low back pain and referred to undergo routine lumbosacral spine MRI examination in the radiodiagnosis and medical imaging department of Menoufia University Hospital. We excluded patients who had undergone a lumbar spine surgery or who have a documented recent spine fracture.

We interviewed the patients to record relevant data: pain analysis (true sciatica, low back pain without radiculopathy, and buttock pain), history of trauma, neoplasm, systemic disease, or medications.

The study was approved by the local research ethics committee of Menoufia University Hospital on November 2019, with reference approval number of 191119RAD 36. All patients gave written informed consents to participate in this study.

Lumbosacral MRI protocol:

All lumbosacral MR examinations were performed on an MRI scanner (1.5 T closed type Toshiba, Excelart Vantage; Sanrad Medical Systems, Bengaluru, India). The patients laid supine, head first. The examinations were done using a dedicated spine coil. Cushions were used for immobilization and extra comfort for legs, and patients were asked to remove metallic objects.

Routine MRI protocol:

The protocol consisted of sagittal T1WI [slice thickness, 4 mm; field of view (FOV), 300 mm; matrix, 216 × 320; repetition time (TR)/echo time (TE), 510/9; and scan duration, 2.24 min], sagittal T2WI (slice thickness, 4 mm; FOV, 300 mm; matrix, 216 × 320; TR/TE, 3000/120; and scan duration, 1.6 min), and axial T2WI (slice thickness, 4 mm; FOV, 230 mm; matrix, 256 × 256; TR/TE, 3000/120; and scan duration, 3 min). Axial images were performed at selected levels chosen from the sagittal sequences, angled through the intervertebral discs.

Additional coronal STIR sequence: a coronal STIR sequence [slice thickness, 5 mm; FOV, 500 mm; matrix, 230 × 256; TR/TE, 4440/41; inversion time (TI), 170; and scan duration, 3.20 min] with large FOV to include the entire abdomen and pelvis was performed and was angulated to include coxo-femoral joints and the sacrum.

Images interpretation and analysis of findings: all images were transferred to a workstation using the Digital Imaging and Communications in Medicine (DICOM) format. For each patient, we evaluated the routine MR protocol images: sagittal T1, sagittal T2, and axial T2 image (later be referred to as set 1) and the routine protocol images in addition to coronal STIR images (later be referred to as set 2). Set 1 images were categorized into (N) normal MRI of the lumbar spine or (P1) positive spinal abnormalities, whereas set 2 images were categorized into (N) normal MRI of the lumbar spine, (P1) positive spinal abnormalities, (P2) positive extraspinal abnormalities, and (P3) spinal and extraspinal abnormalities. The extraspinal abnormalities that were recorded on set 2 images were further studied to determine the frequency of each of them.

Statistical analysis

The collected data were computerized and statistically analyzed using SPSS program (Statistical Package for Social Science) version 26 (IBM, Armonk, New York, USA). Qualitative data were represented as frequencies and relative percentages. χ2 test was used to calculate the difference between qualitative variables as indicated. All statistical comparisons were one tailed, with significance level set as follows: P value less than 0.05 indicates significant.


  Results Top


A total of 300 patients were included in this study (169 males, representing 56%, and 131 females, representing 44%), with mean age of 47 years and age range from 20 to 70 years.

Two sets were evaluated: set 1 represented the routine MRI only, and set 2 represented the routine MRI in addition to coronal-STIR sequences. Scans were evaluated by a radiology consultant (with >15 years of experience in musculoskeletal MRI).

Interpreting set 1 resulted in 122 (40.7%) normal patients, whereas set 2 showed only 74 (24.7%) patients as normal.

On set 2, we could record extraspinal abnormalities through interpreting the additional coronal STIR images in 64 (21.3%) patients, including osteoarthritic abnormalities (n = 25; 39.1%), soft tissue abnormalities (n = 2, 4.5%), neurological abnormalities (n = 4, 6.3%), gynecological abnormalities (n = 31, 48.4%), and miscellaneous (n = 4, 6.3%) [Table 1].
Table 1: Extraspinal abnormalities identified by routine MRI with coronal short TI inversion recovery

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The extraspinal abnormalities were categorized according to their relation to patient's pain into three groups: relevant to patient's pain (n = 18; 29.1%), equivocal (n = 25; 39.1%) and irrelevant to patient's pain (n = 22; 32.8%) [Table 1].

In 18 (6%) patients, we detected extraspinal abnormalities that were believed to explain patients' pain and influence their management plan. These included bilateral sacroiliitis (n = 1), stress fracture of the sacral ala (n = 1) [Figure 1], stress fracture of the proximal femur (n = 1), iliac bone metastases (n = 1), occult pelvic fracture (n = 1), occult intertrochanteric fracture (n = 1), ovarian cyst (n = 5), retroverted uterus (n = 1), simple bone cyst (n = 2), avascular necrosis of femoral head (n = 1), transient osteoporosis of the hip (n = 1), Tarlov cysts (n = 1) [Figure 2], and gluteal muscle tendinopathy (n = 1). Identification of these extraspinal abnormalities was the primary focus of the additional STIR sequence. Extraspinal abnormalities related to patient symptoms depicted on coronal STIR sequence as well as their relation to the presence of spinal abnormalities [Table 2].
Figure 1: A 30-year-old male patient presenting with right sciatica. (a) Routine MR protocol image revealed normal findings with no evident disc lesions or nerve root compression. (b and c) Additional coronal STIR images revealed marrow edema and a stress fracture at the right sacral alum (arrow in b) and thick edematous right S1 nerve root (arrow in c). STIR, short TI inversion recovery.

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Figure 2: A 35-year-old female patient presenting with bilateral sciatica more on the right side. (a) Routine MRI protocol images revealed no disc lesion with no nerve root impingement. (b) Additional coronal STIR images revealed bilateral perineural cysts (Tarlov cysts) along the course of the sacral nerve roots. It was partially visualized on the routine sequences; coronal STIR evaluated its exact extent. STIR, short TI inversion recovery.

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Table 2: Extraspinal abnormalities related to patients' symptoms depicted with coronal short TI inversion recovery sequence

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Regarding the correlation of the presence of extraspinal causes of sciatica with age, in our study, we found that there was no significant association between the age and the presence of extraspinal abnormalities (P = 0.154). Moreover, the presence of extraspinal causes of sciatica was not significantly affected by patients' sex or history of neoplastic disease (P = 0.201 and 0.707, respectively). Conversely, there was a significant association between the presence of an extraspinal cause of pain with absence of spinal abnormalities and nerve root impingement on the routine lumbar MRI (P = 0.049 and 0.021, respectively) [Table 3].
Table 3: Comparison between extraspinal abnormalities and other variables

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  Discussion Top


Sciatica is the most common neurological spine disease [8]. It is defined by low back pain that radiates to the legs, with or without neurologic deficiency [4]. Although most patients with lumbar disc herniation present with sciatica, patients may also present with less common sciatica-like symptoms such as nonradiating low back pain, leg pain, buttock pain, and sensory/motor deficits [9].

MRI is usually the modality of choice when investigating sciatica. The routine MRI protocol of lumbosacral spine focuses only on the lumbar spine and does not provide any information on the lumbosacral plexus or neighboring pelvic girdle, in which the extraspinal causes of sciatica may be seen. A STIR sequence with a coronal view is useful in evaluation of extraspinal causes of sciatica because of its ability to investigate both the bony pelvic girdle and surrounding soft tissues, including the lumbosacral plexus and branches [4].

The aim of this study was to determine the value of coronal STIR sequence in detection of extraspinal causes of sciatica by adding it to routine MRI protocol of lumbosacral spine in patients referred for sciatica-like symptoms.

In the current study, of the 300 patients included, 122 (40.7%) patients were considered normal by reader 1, and 73 (24.3%) patients as normal by reader 2. The rest of the examinations were considered abnormal. Discrepancy in numbers between the two readers can be explained by the fact that some patients who were considered within normal limits by reader 1, using the routine MRI sequences only, had abnormalities in extraspinal locations seen by reader 2 at the coronal STIR sequence.

In this study, the diagnoses by reader 1, using the routine MRI sequences only, were confined to two categories: normal in 122 (40.7%) patients and spinal abnormalities in 178 (59.3%) patients. By analysis of the extraspinal findings that were visible by reader 2 on the coronal STIR sequence, there were some patients who showed extraspinal abnormalities on top of normal lumbosacral spine and others showed extraspinal abnormalities on top of abnormal lumbosacral spine. For this reason, we classified the different diagnoses by reader 2, using both routine and coronal STIR MRI sequences, into four categories: normal in 73 (24.3%) patients, spinal abnormalities only in 163 (54.4%) patients, extraspinal abnormalities only in 30 (10%) patients, and both spinal and extraspinal abnormalities in 34 (11.3%) patients.

In the present study, the extraspinal abnormalities were considered to be related to sciatica or sciatica-like symptoms in 18 (6%) patients. It is important to note that seven of these patients were considered to be normal and seven patients had mild degenerative changes with no significant disc bulge/herniation on routine sagittal and axial protocol. In the remaining four cases, despite the routine MRI revealed significant abnormalities liable to explain the symptoms, the additional coronal STIR also showed significant abnormalities that must be identified and included in the patient's condition for appropriate treatment.

In correlation with previous similar studies, using the same FOV, this percentage was relatively close to the study by Mittal et al.[10] (6.8% of 350 patients), and the same percentage was seen in the study of Laporte et al.[4] (6% of 209 patients).

Six patients of unexpected sacroiliitis were revealed by the coronal STIR sequence in our study: three of them were considered to be normal and the other one had a disc bulge without disco-radicular Impingement. The sciatica-like symptoms due to sacroiliitis may result from two different mechanisms: first, the sacroiliac joint may generate referred pain to the lower limbs because they share the same somatic innervation area, and second, owing to the close relationship between the ventral capsule of the SI joint and the spinal nerves L5 and S1 [11]. Diagnosis of sacroiliitis is frequently unreliable on clinical grounds [12]. Involvement of sacroiliac joint is considered a hallmark for diagnosis of seronegative spondyloarthropathy and is usually the first manifestation of this condition. Thus, detection of sacroiliitis helps in early diagnosis and treatment [13].

Four patients with sacral stress fractures in this study were diagnosed at STIR imaging. One of these patients belonged to the young age group and showed a slightly displaced stress fracture of a sacral wing.

In the current study, hip disorders were identified by the additional coronal STIR sequence and considered as a possible explanation for symptoms in 11 patients, including stress fracture of proximal femur (four patients), stress fracture of sacral ala (four patients), occult intertrochanteric fracture (one patient), transient osteoporosis of hip (one patient), and avascular necrosis of femoral head (one patient). The diagnosis had not been suspected before adding the coronal STIR sequence to routine MRI examination in any of these cases.

Bone tumors, primary or metastatic, located either in the pelvis or at the proximal femur can cause extraspinal sciatica. Previous history of cancer in patients with sciatica, even cancers of uncommon bone metastases, should always be a red flag, where late metastatic lesions from parotid carcinoma, cancer of uncommon bone metastases, have been reported as an extraspinal cause of sciatica 10 years after treatment of primary disease [14]. In our study, three patients were diagnosed as having pelvic bone metastases. One of them was an old male with history of prostatic tumor metastasis. The routine MRI sequences showed vertebral bone metastases, and the coronal STIR sequence also showed iliac wing metastases.

Occult pelvic insufficiency fractures may occur in osteoporotic bone in the absence of trauma or owing to low-energy mechanisms, such as a fall, that would not typically be expected to cause a fracture of the pelvic ring [15]. Often, patients present with intractable low back or pelvic pain and the loss of mobility and independence. Symptoms are exacerbated by weight bearing and relieved by rest [16]. In one patient, presenting with left sciatic pain, in this study, the coronal STIR sequence revealed an occult fracture involving left-sided iliac wing of pelvic bone actually responsible for the symptoms. This fracture was not suspected on routine MRI examination.

In our study, the coronal STIR imaging of a patient referred with low back pain revealed gluteal muscle sprain actually responsible for the symptoms that was not detectable on routine MRI sequences.

Multiple bilateral large Tarlov (perineural) cysts of sacral nerves were identified in four patients with bilateral sciatica. This abnormality, although partially imaged on the axial T2-weighted sequence, was only thought to account for symptoms after reviewing the coronal STIR sequence. These cysts are usually asymptomatic, but enlarged cysts (>1.5 cm), as in our patient, can compress the adjacent nerve fibers and create pain, weakness, and paresthesis [17].

We found that no significant correlation was established between the presence of an extraspinal cause of sciatica and patient's sex. Additionally, use of the additional sequence proved a significant association between the presence of an extraspinal cause of pain with the absence of spinal abnormalities and absence of nerve root impingement on the lumbar MRI. These findings go in line with the study by Laporte et al.[4].

Moreover, our study was in agreement with the study by Laporte et al.[4] regarding the correlation of the presence of extraspinal causes of sciatica with age. In our study, we found that there was no significant difference regarding age groups.

Moreover, in our study, history of neoplasia was statistically not associated with an extraspinal cause of sciatica, and also no association was established between the presence of an extraspinal cause of sciatica and history of neoplasia in the study by Laporte et al.[4].

In our study, we also correlated the presence of extraspinal causes of sciatica with presence of any spinal abnormality. Prevalence of an extraspinal cause of sciatica was significantly correlated with the absence of spinal abnormalities. This finding goes in line with the study by Laporte et al.[4].

In 42 (14%) patients, the coronal STIR in our study also identified soft tissue abnormalities in the pelvis, which may or may not be the cause of patient's pain. The mechanism by which these abnormalities can cause sciatica is the direct compression on the lumbosacral plexus and branches. Because the additional STIR sequence is limited in depicting entrapment phenomena on the lumbosacral plexus and branches, the relation of these abnormalities to patients' pain is still equivocal in our study.

Overall, 31 of these abnormalities were gynecological pathologies, including ovarian cysts, retroverted uterus, and uterine fibroid.

In this study, the coronal STIR sequence identified ectopic pelvic kidney in a patient with low back pain and the routine MRI sequences revealed lumbar spondylosis without disc lesions. A deeply situated ectopic kidney in the true pelvis has been reported by Assadsangabi et al.[18], as a cause of 'sciatica,' probably as a result of impingement on neural structures within the pelvic cavity.

Limitations

The main limitation of the study was that the additional STIR sequence proposed in this study might lack sensitivity in depicting small neuromas or entrapment phenomena on the lumbosacral plexus and branches because of its sequential pattern and high section thickness. Such visualization of nerve injury may be improved by using neurography techniques such as T2-weighted or STIR sequences with maximum-intensity-projection reconstruction or the more recently developed three-dimensional nerve selective techniques based on diffusion-weighted sequences with directional encoding.


  Conclusion Top


Additional coronal STIR images with FOV extending from the mid abdomen down to the femoral lesser trochanters can identify extraspinal abnormalities that are usually overlooked on routine MRI protocol images in patients presenting with sciatica and sciatica-like symptoms.

Our results also showed that extraspinal causes of sciatica are more prevalent in the absence of nerve root impingement on routine protocol images.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Valat JP, Genevay S, Marty M, Rozenberg S, Koes B. Sciatica. Best Pract Res Clin Rheumatol 2010; 24:241–252.  Back to cited text no. 1
    
2.
Yoshimoto M, Kawaguchi S, Takebayashi T, Isogai S, Kurata Y, Nonaka S, et al. Diagnostic features of sciatica without lumbar nerve root compression. Clin Spine Surg 2009; 22:328–333.  Back to cited text no. 2
    
3.
Ergun T, Lakadamyali H. CT and MRI in the evaluation of extraspinal sciatica. Br J Radiol 2010; 83:791–803.  Back to cited text no. 3
    
4.
Laporte C, Albert JD, Duvauferrier R, Bertaud V, Gouillou M, Guillin R. MRI investigation of radiating pain in the lower limbs: value of an additional sequence dedicated to the lumbosacral plexus and pelvic girdle. Am J Roentgenol 2014; 203:1280–1285.  Back to cited text no. 4
    
5.
Brant WE, Helms CA. Fundamentals of diagnostic radiology. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins; 2012.  Back to cited text no. 5
    
6.
Gupta R, Mittal P, Mittal A, Mittal K, Gupta S, Kaur R. Additional merit of coronal STIR imaging for MR imaging of lumbar spine. J Craniovertebr Junction Spine 2015; 6:12.  Back to cited text no. 6
    
7.
Gleeson TG, O'connell MJ, Duke D, Ryan M, Ennis R, Eustace SJ. Coronal oblique turbo STIR imaging of the sacrum and sacroiliac joints at routine MR imaging of the lumbar spine. Emerg Radiol 2005; 12:38–43.  Back to cited text no. 7
    
8.
El Barzouhi A, Verwoerd AJ, Peul WC, Verhagen AP, Ànijeholt GJ, Van der Kallen BF, et al. Prognostic value of magnetic resonance imaging findings in patients with sciatica. J Neurosurg 2016; 24:978–985.  Back to cited text no. 8
    
9.
Al-Khodairy A, Bovay P, Gobelet C. Sciatica in the female patient: anatomical considerations, aetiology and review of the literature. Eur Spine J 2006; 16:721–731.  Back to cited text no. 9
    
10.
Mittal P, Mittal A, Mittal K. Additional merit of coronal STIR imaging for MR imaging of lumbar spine. J Craniovertebr Junct Spine 2015; 6:12–15.  Back to cited text no. 10
    
11.
Buijs E, Visser L, Groen G. Sciatica and the sacroiliac joint: a forgotten concept. Br J Anaesth 2007; 99:713–716.  Back to cited text no. 11
    
12.
Jans L, Van Praet L, Elewaut D, Van den Bosch F, Carron P, Jaremko JL, et al. MRI of the SI joints commonly shows non-inflammatory disease in patients clinically suspected of sacroiliitis. Eur J Radiol 2014; 83:179–184.  Back to cited text no. 12
    
13.
Prabhu S, Irodi A, Prakash D. Seronegative spondyloarthropathy related sacroiliitis: CT, MRI features and differentials. Indian J Radiol Imag 2014; 24:271–278.  Back to cited text no. 13
    
14.
Syggelos S, Megas P, Tyllianakis M. Our experience in extra-pelvic causes of sciatica and review of literature. JSM Neurosurg Spine 2017; 5:1083–1088.  Back to cited text no. 14
    
15.
O'Connor T, Cole P. Pelvic insufficiency fractures. Geriatr Orthop Surg Rehabil 2014; 5:178–190.  Back to cited text no. 15
    
16.
Tsiridis E, Upadhyay N, Giannoudis PV. Sacral insufficiency fractures: current concepts of management. Osteoporos Int 2006; 17:1716–1725.  Back to cited text no. 16
    
17.
Voyadzis J, Bhargava P, Henderson F. Tarlov cysts: a study of 10 cases with review of the literature. J Neurosurg 2001; 95:25–32.  Back to cited text no. 17
    
18.
Assadsangabi R, Hajmomenian M, Nabavizadeh SA, Vossough A. Deep renal ectopia causing sciatic mononeuropathy. Child's Nerv Syst 2014; 30:1759–1761.  Back to cited text no. 18
    


    Figures

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