Clinical issues and challenges in imaging of gastrointestinal diseases: A minireview and our experience

Abstract

Imaging techniques play a crucial role in the modern era of medicine, particularly in gastroenterology. Nowadays, various non-invasive and invasive imaging modalities are being routinely employed to evaluate different gastrointestinal (GI) diseases. However, many instrumental as well as clinical issues are arising in the area of modern GI imaging. This minireview article aims to briefly overview the clinical issues and challenges encountered in imaging GI diseases while highlighting our experience in the field. We also summarize the advances in clinically available diagnostic methods for evaluating different diseases of the GI tract and demonstrate our experience in the area. In conclusion, almost all imaging techniques used in imaging GI diseases can also raise many challenges that necessitate careful consideration and profound expertise in this field.

Key Words: Imaging methods, Gastrointestinal diseases, Gastrointestinal tract, Radiology, Tumors of the gastrointestinal tract

Core Tip: Accurately diagnosing gastrointestinal (GI) diseases mainly relies on imaging the GI tract. With the latest techniques, one can explore the detailed morphology, biomechanical properties, function, and pathology of the GI tract. Technological advancements are happening rapidly, and there is enormous innovation potential. The main developing trends include faster image acquisition, higher resolution, increased computer power, and improved software for post-processing. Additionally, there is a trend towards developing and refining "new sub-modalities" based on traditional methods and fusing different modalities into new multimodal concepts. Overall, the future of GI imaging looks promising and will significantly benefit clinical and research studies of GI diseases.

INTRODUCTION

The imaging of gastrointestinal (GI) diseases is constantly evolving due to the emergence of new technological methods of investigation. However, traditional radiography remains the gold standard in diagnostic imaging. Still, it provides the initial assessment of various critical life-threatening conditions such as bowel perforation, obstruction, volvulus, and inflammatory bowel disease. When a detailed evaluation of the lumen of the GI tract (GIT) is required, fluoroscopic barium or water-soluble single and double-contrast studies have been the studies of choice. However, the latest endoscopic research has also appeared recently, such as wireless capsule endoscopy, which enables direct visualization and intervention in the GIT. Non-invasive imaging methods, including ultrasound, computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI), are increasingly being used in the diagnosis of GIT diseases, including in daily diagnostic practice[1,2].

From an evolutionary point of view, we must note that the most frequently used method in gastroenterology departments is videoendoscopic equipment. However, its application is not limited only to diagnosis. It is also used for therapeutic manipulations of the upper and lower parts of the digestive system - the esophagus, stomach, duodenum (video esophagogastroduodenoscopy), and colon (video colonoscopy)[2].

This minireview aims to summarize the advances in clinically available diagnostic methods for evaluating different diseases of the GIT, describe the advantages and disadvantages of each technological approach, and give relevant evidence, based on our experience, that may improve the diagnosis of GI diseases. We also summarize the advances in clinically available diagnostic methods for evaluating different diseases of the GIT and demonstrate our experience in the area, raising that almost all imaging techniques used in imaging GI diseases can be associated with many challenges that necessitate careful consideration and profound expertise in this field.

GI endoscopy

This procedure is performed to monitor and examine the upper (including the esophagus, stomach, and first part of the small intestine (duodenum)) and lower GIT, using a long, flexible tube called an endoscope[3]. The endoscope has a small light and video camera at one end, and video images from the tube are viewed on a monitor.

The advantages of endoscopic examination include but are not limited to: (1) Taking material for histological examination/biopsy; (2) Removal of polyps; (3) Balloon dilatation in benign and malignant strictures along the course of the GIT; (4) Endoscopic ligament ligation of esophageal varices; (5) Endoscopic hemostasis in acute bleeding; (6) Percutaneous endoscopic gastrostomy in patients unable to eat naturally; (7) Argon plasma coagulation (APC)/APK, a faster and easier method and an alternative to more expensive laser techniques, for destroying the esophagus, stomach, and intestine lesions; and (8) Endoscopic mucosal resection.

Literature data show that endoscopy remains promising for detecting preneoplastic lesions, with some authors determining an accuracy rate of up to 88% for identifying intestinal metaplasia, sensitivity of about 74.6%, and specificity of 94.2%[4-6]. At the same time, this research method is still effective for detecting other GI diseases despite studies that found a poor correlation between macroscopic findings and histopathological diagnosis. In our experience, in about 80% of cases, there is concordance between the endoscopic finding and the histological diagnosis. Therefore, in our opinion, the diagnostic accuracy of the endoscopic research method depends mainly on the endoscopist's ability and the pathologist's competence.

Performing safe endoscopy and turning this method into one of the least invasive methods require that endoscopists understand the potential procedural complications to minimize their frequency and optimize their management. According to literature data, endoscopic activity is increasing rapidly worldwide, evidenced by the annual number of GI endoscopies for adults, which increased by 13.5% from 2017 to 2133541[7]. Unfortunately, at the same time, the number of cases with complications after an incorrectly performed endoscopy is also increasing. For this reason, we hope that this review will serve clinicians practicing in this area as a valuable reference for updating their knowledge.

The following case was carried out on the territory of our departments: Diagnosis and treatment of patients with neoplastic and inflammatory diseases, including inflammatory bowel disease (ulcerative colitis and Crohn's disease). In the case of indications for conducting biological therapy in the hospital, a protocol is drawn up by the National Health Insurance Fund (NHIF), as a team of the Gastroenterology Department is involved in monitoring the patient's condition in the hospital, in accordance with the requirements approved by the NHIF.

In Figure 1A and B, we show endoscopic images of patients with discrete or indeterminate gastroenterological complaints that may be related to irritable bowel syndrome or hemorrhoids. No other test can give a definitive diagnosis. Of course, it should be carried out in the absence of contraindications. In cases like these, a clear idea of localization, patency of the colon, cause of the anemic syndrome, and possibility of taking histology is given. All these contribute to a better diagnosis and more straightforward determination of the choice of behavior.

Figure 1 Endoscopic view of the colon. A: The picture shows a complete loss of haustration and the presence of yellow matter and blood (as an expression of necrosis); B: Complete loss of haustration, absence of vascular pattern, and mucosal glare are also seen; C: Endoscopic view of the ascending colon. The presence of a tumor mass in the ascending colon completely disrupts the structure of the large intestine. Necrosis is clearly visible in the very center, while partial haustration can still be observed in the periphery.

Tumors in the right colon often give late complaints. Even with an advanced tumor, there may be no disturbance in defecation. The most common reason for performing a colonoscopy is anemic syndrome (Figure 1C).

Usually, a definite diagnosis is made after histological examination of a sample obtained during endoscopic evaluation (Figure 2A and B).

Figure 2 Mucinous adenocarcinoma of the colon, with perineural invasion (marked by an arrow). A: The World Health Organization recognized a subtype of colorectal carcinoma with mucin lakes comprising at least 50% of a tumor mass (HE staining, × 100); B: Invasive moderately differentiated adenocarcinoma of the colon (HE staining, × 100).

Narrow band imaging

Narrow band imaging (NBI) is a proven optical technology that allows for a reliable visual diagnosis of all significant indications in the GIT[8]. NBI enables the practical deployment of several strategies for efficient lesion management: Targeted biopsies in the upper GIT, easier decision-making for suitable endoscopic resection techniques, and potentially avoiding histological assessment of low-risk lesions (e.g., diminutive rectosigmoid polyps under the resect and discard paradigm)[8] (Figure 3).

Figure 3 Image showing a mucous membrane with pronounced pavement (a typical picture of Crohn's disease). Narrow band imaging allows looking for visible signs of malignancy - a disturbed pattern, lack of regularity, irregular shape, dark spots in the crypts, and unclear borders. Mucus and residual intestinal contents are represented in red (poor preparation). Edematous mucosa is in blue with a regular pit pattern. Macroscopic signs of malignancy are absent.

Thus, in skilled hands, it is a valuable tool that helps doctors determine the best course of action (endoscopic or surgical) and management. Based on available data, NBI should be routinely used for patients who are at higher risk of developing digestive neoplastic lesions and may soon become the standard of care, at least in referral centers[8]. Adequate training programs are necessary to encourage the integration of NBI into routine clinical practice.

Technological advances in medicine have entirely changed the practice of GI radiology. With the development of high-resolution scanners, it is possible to interpret the disease better, give a more precise assessment of the nature of the disease, the size of the lesions, their relation to the surrounding tissues, and more accurately stage malignant tumor processes.

MRI and CT

In recent years, the development of high-speed sequences and the introduction of diffusion techniques in the examination of the GIT have made MRI a precise tool for staging cancer, most often of the stomach and colon. The ability of MRI to provide optimal soft-tissue contrast and use tissue-specific contrast agents further aid staging. However, MRI is still not a widely accepted standard method for staging cancer of the stomach[9,10].

CT offers new possibilities for imaging inflammatory and non-inflammatory diseases of the GIT by using fine collimation, thus enabling high-quality multiplanar reformation and three-dimensional reconstruction of gastric images. However, proper distension of the stomach and optimal timely administration of intravenous contrast material is necessary for the correct diagnosis of these diseases. Unlike endoscopic examinations of the stomach, CT provides information on both the gastric wall and the extragastric extent of the disease[11]. Several primary GI lesions that are almost pathognomonic are evident in CT features. They have no differential diagnosis and do not require endoscopy or barium confirmation studies. According to data from the literature and our experience, CT has an extremely high specificity in diagnosing both malignant and benign lesions of mesenchymal and epithelial origin. Among some of the most common and probably the most critical nosological entities that are established by CT examination are the following:

(1) Infiltrating scirrhous carcinoma (linitis plastica) presents as a plaque-like or peripheral thickening of the wall, which mimics a benign disease. The division of the intestine is 3-10 mm thick, the affected segment is long (10-15 cm) without sharp transition, and the inner and outer contours of the wall are smooth and symmetrical. Despite its benign appearance, this lesion is easily recognized in the stomach because it frequently affects this organ.

(2) Lymphosarcoma presents as a focal intraluminal lesion or as an infiltrating segmental intestinal lesion leading to slight thickening of the peripheral wall. When focal, it can be misinterpreted as a mesenchymal tumor or adenocarcinoma. It can be mistaken for an inflammatory or ischemic lesion when its involvement is segmental. In most cases, however, there is slight asymmetry in wall thickening.

(3) Diverticulitis: The diagnosis of diverticulitis on CT can be made by a clearly visible symmetrical thickening of the intestinal wall (3-5 mm) in a relatively short segment measuring no more than 4-5 cm. However, proper judgment and differentiation between diverticulum and colon carcinoma are necessary because, according to literature data, in about 10% of patients, there is a significant overlap of colon wall thickness in diverticulitis and carcinoma[11-14].

In addition, different CT and MRI methods play an essential role in diagnosing many abnormalities inside the GIT of the human body, such as CT angiography, which is a valuable imaging technique applicable to the lower GIT and allows fixing the source of acute bleeding in different pathologic conditions of the bowels[15].

PET and MRI enterography

PET and MRI enterography are novel hybrid imaging techniques that assess and treat inflammatory disorders of the GI system, such as inflammatory bowel disease. By origin, it is a combination of the image between metabolic information of PET imaging scanner with the spatial resolution and soft tissue contrast of MR imaging scanner[16].

Also, MRI as a technique plays an essential role in diagnosing patients suffering from liver diseases. MRI gives multiparametric imaging data without any radiation exposure. T2-weighted imaging (T2WI), as a subtype of MRI examination, is an essential method for detecting and characterizing focal liver lesions, such as neoplasms with different origins. Several problems are manifested by this imaging method, and most important are the long acquisition time and motion artifacts during the examination. Multiple breath-hold T2WI based on fast spin echo increases the diagnostic performance. It reduces the negative outcomes of the previous technique[17].

18F-fluoro-2-deoxyglucose (FDG)-PET/CT is an imaging technique using the combination of standard PET or standard CT in combination with intake of [18F] FDG, a radiopharmaceutical compound, which is a marker for the tissue uptake of glucose, closely correlating with certain types of abnormal tissue metabolism in a specific type of neoplasms.

This imaging method is helpful in cases of suspected neoplasm of the liver and the pancreas, showing abnormal foci of radioactive fluoro glucose intake inside the tissues. A weak part of the examination should be an artificial higher FDG activity in the bowel in patients with metformin therapy. Also, this method is not primarily helpful in determining neuroendocrine tumors and small bowel tumors[18].

Molecular imaging

Molecular imaging techniques combined with CT/MRI examination should significantly affect the diagnosis and prognosis of many GI diseases. PEGylated BaGdF5 nanoparticles as contrast agents could be considered for GI disease diagnosis and prognosis processes in the near future, allowing easy, informative, and safe examination of the stage and the prognosis of different GI abnormalities[19].

Current clinical molecular imaging approaches primarily use PET- or single-photon emission CT-based techniques where novel molecular targets of various diseases are identified and multifunctional contrast agents for imaging these molecular targets are developed. In such a way, new technologies and instrumentation can be employed for multimodality molecular imaging. Furthermore, in vivo molecular imaging has a great potential to impact medicine by detecting diseases in early stages (screening), identifying extent of disease, selecting disease- and patient-specific therapeutic treatment (personalized medicine), applying a directed or targeted therapy, and measuring molecular-specific effects of treatment[19].

Recent preclinical research and technological developments in instruments like endoscopes and microcatheters indicate that these molecular imaging modalities (i.e., contrast-enhanced molecular ultrasound, optical imaging with fluorescent molecular probes, Raman spectroscopy/microscopy, and photoacoustic imaging) may soon be used in clinical settings and have a wide range of clinical uses[19].

Recent advances and unresolved issues regarding imaging of GI diseases

Although the GIT was considered difficult for evaluation with imaging, recent techniques revolutionized the investigation of GIT: GIT contrast studies, enterography and enteroclysis, ultrasound, and cross-sectional imaging modalities, such as CT, MRI, and PET-CT/MRI[20].

Moreover, with the constant development of advanced imaging technology, we can expect to see improvements in the resolution of imaging data. Techniques such as 3D acquisition, filtering, enhancement, segmentation, and tissue classification are being refined to provide more accurate diagnoses. Additionally, co-registration techniques allow for the acquisition of multimodal data, which can further enhance the classification of tissue pathology. These technological advancements will surely cement gastroenterology as a distinct medical specialty[21].

In Table 1, we present the main current limitations related to GI imaging techniques.

Table 1 Main limitations/difficulties, approaches to improve them, and benefits/advantages of gastrointestinal imaging techniques available currently.

	Limitations and difficulties	Approaches to improve the limitations	Benefits and advantages	Ref.
Fluoroscopy of the GIT with contrast media	Direct visualization of the lumen and mucosa only	Digital fluoroscopy has been introduced to reduce the dosage and better the image quality	High temporal and spatial resolution	[24,25]
	High radiation exposure		Fast image acquisition
	No postprocessing possible		Using intraluminal contrast, the function can be assessed – i.e., motility
	Patient cooperation is needed		The only method that can show swallow reflex
	Contraindicated in case of acute bleeding and perforation
Ultrasound	High doctor expertise is needed	The technique of strain rate imaging by Doppler allows for obtaining a detailed description of the walls	Ideal for image-guided interventions	[26-30]
	Patient preparation is needed	Contrast-enhanced ultrasound has a role in identifying hypervascular tumors and wall hyperemia and edema in case of inflammation	High resolution for soft tissues
	Difficult for interpretation artifacts	The bowel walls are assessed with high-frequency endosonography	Suitable for repeated examination and research due to no radiation exposure
	Total visualization of the entire intestines is impossible	During contractions of the GIT musculature, the cross-sectional area of the outer longitudinal muscle increases – this was shown in endosonography	Intestinal wall and intraluminal evaluation
			Information of function – i.e., motility and flow
Endoscopy	Invasive procedure that requires preparation	Chromoendoscopy – betters the image quality by adding colors	Direct visualization of the mucosal surfaces	[31-33]
	Risk of perforation, bleeding, and other procedure-related complications	Virtual chromoendoscopy – addition of "missing colors"	Intervention – i.e., biopsies, polypectomy, endoscopic surgery
	No visualization of deeper layers and surroundings	Filters (i-scan, SPIES, FICE) - alter the wavelength ranges of reflected light
		Capsule endoscopy – better patient tolerance
Multidetector computed tomography	High radiation exposure	New software reconstruction options – virtual colonography, unfolding and dissection of the intestinal wall, and computer-aided detection improve the diagnosis	Fast image acquisition, fewer motion artifacts	[34,35]
	No direct information on the function		Evaluation of total intestines and surroundings
	Less suitable for healthy subjects' examination		3D reconstructions and virtual endoscopy
	Risk of contrast-induced nephropathy in patients with kidney function impairment		High temporal and spatial resolution
Magnetic resonance imaging	3D reconstructions and virtual endoscopy (lower image resolution than CR)	Motion artifacts can be overcome by applying spasmolytics	Suitable for soft tissues	[36-40]
	Long image acquisition	Optimal distention of the bowel walls can be reached by applying water-soluble contrast materials with hyperosmotic agents, such as polyethylene glycol, methylcellulose, and mannitol	Ideal for repeated examination and research due to no radiation exposure
	Motion artifacts due to intestinal motility	Inflammatory changes in the bowel walls are better shown in contrast-enhanced studies	Evaluation of total intestines and surroundings
	Potentially long-term adverse effects of gadolinium-based contrast media (risk of nephrogenic systemic fibrosis development)	GIT function is shown by functional cine-magnetic resonance imaging	Information of function – i.e., motility and flow
		Development of resonance imaging colonography is in the process
		Patient preparation is needed to avoid false positive results because of intestinal residual stools. Bowels need to be filled with water.
		New postprocessing techniques have been introduced, such as 3D models of the properties of the intestinal walls
PET	High radiation doses	PET in combination with CT – PET/CT allows the use of both methods, thus usage of their benefits	PET enables visualization of metabolic changes, which can precede structural transformation	[18, 41-44]
	Only useful in case of tumors
	Lower spatial and temporal resolution compared to CT
Impedance planimetry known as Functional Lumen Imaging Probe	Not directly applicable to GI distension studies	Modifications in terms of dimensions, electronics, signal processing, and distension protocols are needed to improve the image	Allows direct online imaging of the luminal geometry of the GIT	[45-49]
			Suitable for visualization of the complex physiology of the GI sphincters
Oesophageal high-resolution manometry	Provides insufficient explanation of non-obstructive dysphagia	Probably, the esophageal stress tests add value	Allows online visualization of oesophageal peristalsis	[50-55]
	No sufficient data on specific factors (i.e., technique and patients) impact the measurements	Panesophageal pressurization during multiple rapid swallows is a sign of true stasis, justifying a diagnosis of achalasia	High accuracy in oesophageal motor dysfunction visualization
	More expensive than conventional manometry (i.e., equipment and maintenance costs)
Scintigraphy and single photon emission computed tomography	Low radiation burden	N/A	For emptying and motility studies of the GI conditions	[56-60]
	Long scan times and low-resolution images prone to artifacts and attenuation		Can localize bleeding, especially in patients with a history of previous operations or cancer
	Some artifacts can mimic perfusion defects		Can quickly detect altered anatomy and bleeding from the tumor or operation site
	Does not provide a quantifiable estimate of the blood flow, unlike PET		Useful for guiding surgeons for more accurate localization
			Provides information on the oesophagus
			Scintigraphy with a radiolabeled somatostatin analogue (the gold standard for evaluating gastric emptying in patients with dyspepsia)

Technological advancements in endoscopy have greatly improved the diagnosis of digestive disorders. GI: Gastrointestinal; GIT: GI tract; SPIES: Storz professional image enhancement system; FICE: Fujinon intelligent chromoendoscopy; CR: Computed Radiography; PET: Positron emission tomography; CT: Computed tomography.

Technological advancements in endoscopy have greatly improved the diagnosis of digestive disorders in recent decades. This progress has allowed gastroenterologists to provide more precise diagnoses, cementing gastroenterology as a distinct medical specialty[22].

It is imperative to provide training for advanced endoscopic imaging of GI diseases. Although several web-based educational programs exist, Hoogenboom et al[23] demonstrated training limitations in advanced imaging techniques. Learning curves post-training are steep for web-based and didactic training programs. However, no data on the expert level after training was found. The training programs should focus on developing advanced techniques and be standardized and broadly implemented. Additionally, artificial intelligence-assisted endoscopy should be evaluated[23].

The potential for advancements in GI imaging technology is promising and could greatly benefit both clinical and research studies of GI diseases. We expect to see even more accurate diagnoses with continued refinement of 3D acquisition, filtering, enhancement, segmentation, and tissue classification techniques. Additionally, co-registration techniques to acquire multimodal data can further enhance the ability to classify tissue pathology. These developments will solidify the importance of gastroenterology as a distinct medical specialty[21].

The accurate diagnosis of GI diseases mainly relies on imaging the GIT. With the latest techniques, one can explore the detailed morphology, biomechanical properties, function, and pathology of the GIT. Technological advancements are happening rapidly, and there is enormous innovation potential. The main developing trends include faster image acquisition, higher resolution, increased computer power, and improved software for post-processing. Additionally, there is a trend towards developing and refining "new sub-modalities" based on traditional methods and fusing different modalities into new multimodal concepts. Overall, the future of GI imaging looks very promising and will significantly benefit clinical and research studies of GI diseases[21].

CONCLUSION

In conclusion, we could mention that whenever methods are used to visualize the various inflammatory and tumor lesions of the GIT, the main aim is to make an early diagnosis, which will benefit early treatment and a better prognosis. Despite expensive technological methods for imaging the lesions of the GIT, video endoscopy is still the primary step in the detection. CT or other methods can characterize the diseases, and finally, a biopsy should be performed for the final and most accurate diagnosis. Because all these imaging procedures are complex and insensitive to early lesions, the biopsy is ultimately the "gold standard" for diagnosis. Furthermore, technological advancements in GI imaging hold great promise for improving the quality of clinical and research studies related to GI diseases. As 3D acquisition, filtering, enhancement, segmentation, and tissue classification techniques continue to be refined, even more accurate diagnoses are anticipated. Further improvements in the ability to classify tissue pathology can be achieved through co-using many techniques to acquire multimodal data. These developments will further solidify the importance of gastroenterology as a distinct medical specialty. The most important aspect of diagnosing GI diseases is imaging the GIT, and with the most recent techniques, one can investigate the intricate morphology, biomechanical properties, function, and pathology of the GIT.