Imaging findings of irritable bowel syndrome patients, and the diagnostic value of irritable bowel syndrome: A systematic review

Abstract

BACKGROUND

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal (FGITD) disorder, the diagnosis is based on Rome Criteria and other subjective tools. Because IBS overlaps with other FGITD and organic diseases, and the subjective tools do not apply to patients with cognitive decline, objective diagnostic tools are important in this category of patients.

AIM

To discuss the role of imaging in IBS diagnosis.

METHODS

We systematically searched three databases for articles published in the English language with no limitation to a specific period. The literature search was conducted in June and July 2024. The keywords used are IBS and functional bowel disorders, computed tomography, Magnetic Resonance Imaging, functional brain magnetic resonance imaging (MRI), and static brain MRI, and were linked with the terms ^"AND" and ^"OR". Out of the 679 articles, 578 remained after duplication removal. However, 50 full texts were used in the review.

RESULTS

Magnetic resonance imaging is superior due to its sensitivity, lack of radiation exposure, and lack of need for bowel preparation. Patients with IBS had smaller colonic and rectal volumes compared to healthy controls and functional constipation. Dynamic and static Magnetic Resonance Imaging of the brain showed increased activity, thinning, and increased volumes in specific areas of pain modulation. The above abnormalities are not uniform and vary significantly according to the type of IBS, the duration and intensity of symptoms, gender, and culture.

CONCLUSION

Magnetic resonance imaging shows smaller colonic and rectal volumes, and increased activity, thinning, and increased volumes in specific areas of pain modulation. Large trials incorporating all above limitations are needed.

Key Words: Irritable bowel syndrome; Diagnosis; Magnetic resonance imaging; Ultrasound; Computed tomography

Core Tip: Irritable bowel syndrome (IBS) is a prevalent brain-gut axis disorder, however, the diagnosis is based mainly on Rome Criteria which concentrates on the gastrointestinal tract with ignorance of the brain-gut axis. Furthermore, the Rome criteria are not suitable for patients with cognitive decline. Therefore, tools to address the above diagnostic gaps are highly relevant. In this review, we gave a broader insight into the role of abdominal and brain imaging in diagnosing IBS. The findings, the difference between diarrhea-predominant and constipation-predominant IBS, gender, geography, and cultural background, and the pros and cons of different imaging were discussed.

INTRODUCTION

Irritable bowel syndrome (IBS) is among the most prevalent disorders of gut-brain cross-talk. The diagnosis of IBS is based largely on the Rome Criteria which are subjective and were developed in the Western countries. Therefore, they cannot be generalized to other parts of the world with different cultures[1].

Due to its chronic nature, its mental and organic impact, and the high prevalence, IBS socioeconomic burden is high, and its effects on the patient's quality of life are significant. In addition, the issue of IBS is dynamic and the understanding of the syndrome is rapidly changing because of the recent advances in relevant clinical research[2]. The prevalence of IBS varies significantly and depends on the methods of diagnosis, Geography, and culture. The Rome Foundation Global Study reported a prevalence of 10.1% and 3.8% when using Rome III, and Rome IV respectively. Importantly, the change in the dynasty of symptoms, the suggestion by the Rome IV Criteria to include the gut-brain interaction, and the overlap with other functional gastrointestinal syndromes have encouraged research in this field[2-4].

ROME 1V Criteria are more restrictive, less likely to diagnose unspecific symptoms, and milder for IBS. Therefore, they are more helpful in tertiary care centers, unlike the ROME III Criteria. Other limitations of the ROME Criteria are overlaps with organic diseases including chronic overlapping pain conditions[5], inflammatory bowel disease[6], and endometriosis, which are concerning[7]. In addition, some nations are less likely to express pain (Asians) bloating/distension. Therefore, IBS could be underestimated[8]. Similarly, the distorted body image and self-criticism created by IBS were thought to mediate the association between IBS, anxiety, and depression[9].

IBS encompasses a wider spectrum of gastrointestinal, extraintestinal, and psychological comorbidities. Because of this, other methods incorporating features other than stool consistency and forms are needed[10].

IBS is a chronic burdensome disorder that is usually misdiagnosed as another condition leading to delayed diagnosis and treatment. The delayed diagnosis of IBS substantially disturbs the quality of life of patients and increases the healthcare cost[11]. Positive diagnostic methods rather than the reliance on exclusion and ROME Criteria are highly needed for a better understanding of the disease and the introduction of multimodal treatment[12].

Because of the established association between IBS, psychological distress, and organic disease, imaging is justifiable in selected patients. Likewise, IBS patients ≥ 50 years old are at an increasing risk of dementia[13], and Rome Criteria might not be applicable among patients with cognitive decline. On the other hand, The United States, and United Kingdom suggested no radiological imaging for IBS diagnosis unless red flags are present. The radiological procedure depends on the most likely alternative diagnosis[14] because evidence shows that colonoscopy, barium enema, and ultrasound yield is low regarding structural changes (diverticulosis, inflammatory bowel disease, and colorectal cancer)[15]. Likewise, psychological stress could affect gut function and brain visceral sensitivity which is the case of IBS[16]. Functional imaging including magnetic resonance imaging (fMRI) and positron emission tomography (PET) significantly advanced our knowledge about gut-brain interaction in particular among patients with IBS. An interesting study used functional near-infrared spectroscopy to assess brain activity among patients with functional dyspepsia, IBS, and healthy control subjects in response to food images. The authors concluded that there was higher prefrontal cortex activity among patients with functional dyspepsia than among their IBS counterparts[17]. Therefore, imaging including abdominal ultrasound, computed tomography (CT), and MRI (abdominal or brain diffusion) could be justifiable in selected patients with cognitive decline and alarm features, in contrast to the subjective Rome Criteria. The current review aimed to discuss the role of imaging in IBS diagnosis.

MATERIALS AND METHODS

Setting

The current diagnosis of IBS with the ROME Criteria with the reliance on abdominal pain, stool form, and consistency has several limitations because several nations are less likely to express pain but fullness/bloating. In addition, IBS is a wider disease with internal and extra-intestinal symptoms and a great overlap with psychological disorders. Furthermore, ROME Criteria are not working among patients with cognitive decline.

This review was conducted in June and July 2024 with strict adherence to the PRISMA Guidelines to fulfill the objectives which are the role of imaging including ultrasound, CT, and MRI in IBS diagnosis.

Inclusion criteria

The inclusion criteria were Cross-sectional studies, retrospective and prospective studies, randomized trials, and case-control studies conducted on humans were approached. The studies were included if they used abdominal ultrasound, CT, and MRI to diagnose IBS. In addition, brain MRI, structural, and function among patients with IBS were approached.

Exclusion criteria

Case studies, opinions, editorials, and protocols without data were not. Barium studies, radionuclide studies, and colonoscopies were not included. Brain imaging was confined to MRI, therefore, CT brain with its different modalities was also excluded.

Outcome measures

The outcome measures were colonic diameters and transit time, and the static and dynamic changes of the brain MRI.

Literature search

We searched PubMed/MEDLINE, Google Scholar, and Cochrane Library for articles assessing the role of imaging as a diagnostic measure for IBS. The literature search was limited to the articles published in the English language with no limitation to a specific period. The keywords IBS and functional bowel disorders, CT, MRI, functional brain MRI, and static brain MRI were used and linked with the terms ^"AND" and ^"OR". The total hits in the above databases were 679 articles, and 578 remained after duplication removal. In the current review, 50 full texts were screened and used in the introduction and article text (Figure 1).

Figure 1  Literature search to retrieve articles assessing the role of imaging in the irritable bowel syndrome diagnosis (The PRISMA Chart).

Data extraction

An Excel sheet was used to extract the author's name, year and country of publication, type of study, age, gender, number of participants, and the main results of the imaging procedure (Table 1).

Table 1 Basic characteristics and imaging results among patients with irritable bowel syndrome, mean ± SD.

Ref.	Country	Study design	Sample size	Age/years	Females, %	Main result
Klinge et al[19], 2022	Denmark	Case-control	20	25-53	76%	Low colonic volume and rapid transit time among IBS patients compared to chronic constipation
Lam et al[20], 2016	United Kingdom	Case-control	48	27-53	91.3%	Higher ascending colon volume in functional constipation compared to IBS patients
Pritchard et al[21], 2014	United Kingdom	Case-control	50	39 ± 13	58.7%	Less ascending colon postprandial volume and high descending colon volume among IBS compared to healthy controls
Di Palma et al[28], 2011	Italy	Case-control	40	31 ± 7	66.7%	Rectal volume was smaller among IBS patients
Nilsson et al[34], 2015	Denmark	Cross-sectional	25	Not mentioned	All males	No inter-individual and intra-individual variability in colonic volume MRI
Grinsvall et al[38], 2021	Sweden	Case-control	354	27.9 ± 9.9	All females	Low grey matter volume in the posterior insula and superior frontal gyrus with high grey matter volume and cortical thickness in the somatosensory cortex and subcortical regions
Blankstein et al[39], 2010	Canada	Case-control	27	30.85 ± 8.9	All females	Increased gray matter in hypothalamus among patients with IBS, and anterior midcingulate cortical thinning
Chua et al[40], 2017	Taiwan	Case-control	69	36.7 ± 7.7	All females	Supramarginal cortex, middle frontal cortex, and left cuneus showed cortical thinning in IBS patients with a negative correlation with the disease severity
Jiang et al[42], 2013	United States	Case-control	266	34.72 ± 11.12	84.6%	No difference in cortical thickness between IBS patients and control subjects. Cortical thickness decreases in the bilateral subgenual anterior cingulate cortex, and increases in the somatosensory and primary motor cortex among women with IBS
Mao et al[43], 2020	China	Cross-sectional	68	Not mentioned	Diarrhhea predominant subjects	Enlarged caudate nucleus and thalamus, and altered hemispheric asymmetries among diarrhea-predominant IBS patients
Chen et al[44], 2011	Canada	Cross-sectional	26	20-54	All females	Mean fractional anisotropy was observed in IBS patients in the fornix and external capsules
Zhao et al[45], 2018	China	Case-control	30	77.5 ± 6.3	20%	Gray matter volume is low in occipital and frontal lobes, limbic and hippocampus, and high in angular and temporal gyrus, and insula
Icenhour et al[50], 2017	Sweden	Case-control	61	32-36	All females	Resting-state functional connectivity is reduced in the amygdala and insula in IBS patients
Guleria et al[51], 2017	India	Case-control	20	30.5	All males	Homeostatic emotions, autonomic responses to pain, and affective motivation differ in IBS patients compared to controls

IBS: Irritable bowel syndrome; MRI: Magnetic resonance imaging.

Risk of bias assessment: We used the Newcastle Ottawa Scale to assess the quality of the included studies[18] (Table 2).

Table 2 Risk of bias assessment of the included studies.

Ref.	Selection bias	Comparability bias	Outcome	Total score
Klinge et al[19], 2022	3	1	3	7
Lam et al[20], 2016	4	2	3	9
Pritchard et al[21], 2014	3	1	3	7
Di Palma et al[28], 2011	3	2	2	7
Nilsson et al[34], 2015	3	2	2	7
Grinsvall et al[38], 2021	4	2	3	9
Blankstein et al[39], 2010	3	2	3	8
Chua et al[40], 2017	3	2	3	8
Jiang et al[42], 2013	3	2	2	7
Mao et al[43], 2020	3	2	3	8
Chen et al[44], 2011	3	2	2	7
Zhao et al[45], 2018	3	2	3	8
Icenhour et al[50], 2017	3	2	3	8
Guleria et al[51], 2017	3	2	2	7

RESULTS

Characteristics of the included studies

The current review results were based on 14 studies, 7 studies were from Europe, 4 from Asia, two were published in Canada, and one from the United States. The studies included 1104 participants, and the majority were females. All the studies were observational studies (11 case-control and 3 were cross-sectional) with good quality (Figure 1, Tables 1 and 2).

DISCUSSION

Abdominal imaging changes in IBS

Colonic volume and transit time: MRI showed low colonic volume and rapid transit time among patients with IBS compared to chronic constipation and healthy control subjects[19] supporting a previous study conducted by Lam et al[20] who found higher ascending colon volume in functional constipation. More studies confirmed the above findings and attributed the findings to increased sensitivity to colon distention in patients with IBS because both constipation and diarrheal IBS had increased rectal sensitivity and less call for stool[21-24]. Importantly, there is substantial intra and inter-individual variation that should be controlled for before reaching a firm conclusion[25]. In addition, the colonic volume changes are not uniform through IBS spectra, Pritchard et al[21] observed a rise in ascending colon volume and a decrease in the descending colon following a meal in constipation-predominant IBS and healthy subjects suggesting a retrograde movement from the left colon[26], the reverse happen later. By contrast, the retrograde movement is not observed in diarrheal-predominant and mixed IBS[27]. Similarly, MRI showed smaller rectal volume among patients with IBS suggesting an increased tone in the resting state[28].

The current evidence of low colonic volume among patients with IBS is promising for the classification of colonic disorders. Future research to investigate whether patients with larger colonic diameters respond better to prokinetics or laxatives. MRI studies could help further the classification of patients and treatment guidance[27,28]. In addition, the separation of the colonic content (gas, fluid, or solid) using postprocessing of MRI could be helpful for the individualization of therapy (drug/diet)[29]. However, the current evidence was based on observational studies with female predominance which are more prone to bias. In addition, the MRI is not cost-effective and is not available in the primary care setting.

Regarding the colonic transit time, less transit time was reported among IBS compared to functional constipation, however, the study was performed after laxative stimulation and not under normal conditions[20]. A previous study[30] used radiopaque markers and found low transit time among patients with IBS compared to patients with diarrhea and constipation. Radiopaque markers and colonic scintigraphy although useful, radiation exposure is a big limitation[31].

Other attractive imaging are ultrasound and CT which can provide structural evidence. Ultrasound studies on IBS patients showed increased gallbladder and colon contractility with impaired pyloric and stomach contraction and transit, hyperechoic rectum with acoustic shadow is characteristic[32]. However, ultrasound is operator–dependent and is not sensitive to colonic volume evaluation, and CT radiation exposure is a major limitation[33]. Therefore, MRI is more attractive in the diagnosis of IBS and functional constipation, because it is sensitive, no need for bowel preparation, and no radiation exposure (a big advantage since most IBS patients are females of reproductive age)[34].

The diagnostic value of brain imaging changes in IBS patients

The gut-brain interaction: The pathophysiology of IBS is complex where gastrointestinal tract (GIT) symptoms are induced by any combination of visceral hypersensitivity, motility disorders, disturbance in mucosa and immunity, and altered gut microbiota diversity and function[35]. Interoceptive signals originate from the GIT and memories for them are extensively modulated by cognition, emotion (depression and anxiety), and motivational factors. Therefore, the pathophysiology is wide and involves the GIT (gut connectome), wide areas of the brain (brain connectome), and input from the autonomic nervous system, and neuroendocrine[36]. The multifactorial nature of IBS makes the diagnosis challenging, there is a need for objective measures to address the brain static and dynamic change to assist the diagnosis, suggest future research, and guide IBS therapy.

Rectal nociception and MRI brain abnormalities: The gut-brain connections are not only important in food digestion, but also related to mood disorders, stress, altered bowel motility, and abdominal pain, because of that rectal inflation among patients with IBS activates the emotion arousal, attention, and visceral sensation areas of the brain[37].

Higher cortical thickness and grey matter volume in the somatosensory cortex and subcortical regions were found among women with IBS, the reverse was observed in the superior frontal gyrus and posterior insula[38]. Blankstein et al[39] used functional MRI and found high grey matter volume in the hypothalamus with thinning in the anterior midcingulate might be related to continuous stress and activation of the hypothalamic-pituitary-adrenal axis. Chronic abnormal input from the GIT or pre-existing brain abnormalities that predisposed to IBS could explain the findings. Importantly, Chua et al[40] confirmed the cortical thinning, but with a negative correlation with the duration and severity of abdominal pain. The contradiction in the above results could be explained by cultural and gender disparities in pain perception[41], people from the East are more tolerant of pain compared to their counterparts from the Western region and females tolerate pain more[42].

Enlarged caudate nucleus and thalamus were observed in diarrhea-predominant IBS with thalamic rightward asymmetries and leftward asymmetries in the caudate nucleus in contrast to the finding in the healthy controls[43]. Chen et al[44] conducted a study among IBS females and showed higher mean fractional anisotropy in the insula and fornix while matter compared to their counterparts without the syndrome. Zhao et al[45] conducted a study among elderly IBS patients, structural MRI, diffusion tensor imaging analysis, and Voxel-based morphometry studies supported by Blankstein et al[39] and Chen et al[44]. An important finding with clinical implication is the association between depression and similar cortical thinning observed in IBS, additionally, depression is prevalent among IBS patients[46,47]. Hence, some tricyclic antidepressants might be an effective therapy for IBS[48].

Brain resting state activity in IBS: The resting state brain activity among patients with IBS differs significantly from healthy volunteers, high activity resting state was observed in wide areas including the postcentral gyrus, frontal, and temporal lobe. In contrast, the cingulate and paracingulate gyrus showed decreased resting state activity. Importantly, resting-state functional connectivity is related to visceral sensitivity and symptom severity[49,50]. Interestingly, the brain activation is different in constipation and diarrheal-predominant IBS[51].

Only English literature should be included, and various screening criteria resulted in a small number of articles being included.

CONCLUSION

Patients with IBS had smaller colonic and rectal volumes compared to healthy controls and functional constipation. Dynamic and static MRI of the brain showed increased activity, thinning, and increased volumes in specific areas of pain modulation. High colonic diameter and decreased transit time detected by MRI are promising for the diagnosis of IBS due to its sensitivity, lack of radiation exposure, and lack of need for bowel preparation. Imaging could be beneficial for the diagnosis of IBS among patients with alarm symptoms and cognitive dysfunction because Rome Criteria are subjective and need patients' responses. Imaging results could direct response to specific IBS treatment (diet/medications). The above abnormalities are not uniform and vary significantly according to the type of IBS, duration, intensity of symptoms, gender, and culture. Because of that, high patient selection is needed. Large trials incorporating all IBS subtypes, both women and men and controlling for sociodemographic and cultural factors are needed.

ACKNOWLEDGEMENTS

We want to acknowledge the Saudi Digital Library for accessing the databases.