Gastrointestinal [GI] tract ailments encompass a common and diverse group of diseases that are prevalent in various populations, with inflammatory bowel disease being a common chronic and recurrent condition affecting over 1.2 million Americans and showing an increasing incidence in other populations ^[1][2][1,2]. In the past, endoscopy and fluoroscopy were the primary diagnostic tests for GI tract assessment. However, these techniques have limitations in evaluating the submucosal layers of the bowel wall and are invasive, which may be suboptimal when repeated studies are needed over time ^[3][4][5][6][3,4,5,6]. Currently, cross-sectional imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) are considered the preferred modalities for assessing the bowel wall. Ultrasound has also demonstrated a limited role in assessing the bowel wall. Numerous studies have demonstrated the performance of imaging GI tract modalities such as computed tomography (CT) ^[7][8][7,8], magnetic resonance imaging (MRI) ^[3][9][3,9], and photoacoustic tomography (PAT) ^{[10][11][12][13][14]}[10,11,12,13,14]. However, these techniques provide anatomic imaging but lack functional information. Molecular imaging, which is a diverse field encompassing various modalities, has the potential to provide additional functional information that can aid in guiding management decisions. Recent developments in molecular imaging have focused on improving and combining modalities to create more sophisticated imaging approaches. Imaging of the GI tract plays a crucial role in the diagnosis and treatment of chronic GI diseases. Multiple imaging modalities are available for GI tract imaging, including MRI, PET, SPECT, ultrasound (US), and PAT. On one hand, these imaging modalities can provide us with accurate information; on the other hand, these come with inherent limitations such as limited spatial resolution, poor sensitivity, contrast agents, or radiation exposure.

2. X-ray/CT

X-ray and computed tomography (CT) are imaging techniques that have seen significant advancements in recent years. These advancements have led to improved sensitivity, reduced exposure time, and decreased patient radiation dose in X-ray imaging. CT, in particular, has become a widely used imaging modality for diagnosing diseases of the gastrointestinal (GI) tract due to its high diagnostic accuracy for most GI indications. CT, which involves the emission and detection of X-rays, offers high per-slice acquisition rates and scans with a total exposure of less than 1 mSv, alleviating concerns about radiation exposure compared to previous techniques [15]. CT has become commonly used for detecting structural abnormalities such as tumors and fibrosis, as well as diagnosing conditions of the chest, abdomen, and upper GI tract ^[2][16][2,16]. In contrast to X-ray imaging, which has seen a decline in use for GI tract indications, CT has become a preferred choice for many clinicians due to its superior diagnostic accuracy and reduced radiation exposure. The advancements in CT technology have made it a valuable tool in the diagnosis of GI diseases, allowing for improved visualization and assessment of the GI tract with minimal radiation risk to patients.

3. MRI

Magnetic resonance imaging (MRI) is another powerful imaging modality that has gained popularity in recent years for evaluating diseases of the GI tract ^[17][18][17,18]. Unlike X-ray and computed tomography (CT) which utilize ionizing radiation, MRI employs powerful magnets and radio waves to generate detailed images of the internal structures of the body without exposing patients to harmful radiation ^[19][20][19,20]. MRI offers several advantages for GI imaging, including its ability to provide high-resolution images of soft tissues, such as the GI tract, allowing for detailed visualization of anatomical structures and functional assessment [21]. MRI can also provide valuable information about blood flow, inflammation, and tissue characteristics, making it particularly useful for evaluating conditions such as Crohn’s disease, ulcerative colitis, and tumors in the GI tract [22]. MRI is considered especially valuable in evaluating the small bowel, as it can provide detailed images of the intestinal wall, detect inflammation, and assess the presence of strictures or fistulas [23]. Additionally, MRI with contrast enhancement using gadolinium-based contrast agents can help improve the visualization of lesions and enhance the diagnostic accuracy of GI diseases [22]. Although MRI has some limitations, such as its relatively higher cost and longer acquisition times compared to other imaging modalities, its non-invasive nature, lack of ionizing radiation, and excellent soft tissue contrast make it a preferred choice for many clinicians in the evaluation of GI diseases, especially in cases where detailed anatomical and functional information is required.

4. PET/SPECT

PET (positron emission tomography) and SPECT (single-photon emission computed tomography) are nuclear medicine imaging techniques that are used in combination with other imaging modalities that rely on the use of radiolabeled antibodies or markers, such as identifying body glucose uptake [24]. PET imaging involves the use of a radioactive tracer that is injected into the patient’s body while SPECT uses a gamma camera to detect the gamma rays emitted by a radioactive tracer that is injected into the patient’s body. PET is particularly useful in detecting metabolic changes in tissues, which can help identify areas of increased activity, such as tumors or areas of inflammation. SPECT is commonly used in combination with CT or MRI to provide functional and anatomical information in the evaluation of GI diseases ^[20][25][20,25]. PET and SPECT can be utilized in the evaluation of a wide range of GI conditions, including cancer staging, assessment of treatment response, and detection of recurrent disease [26]. They can also provide valuable information about blood flow, metabolism, and molecular changes in tissues, allowing for early detection and monitoring of disease progression. One of the advantages of PET and SPECT is their ability to detect functional changes in tissues before structural changes are evident, making them valuable tools in the early detection of GI diseases, which can help guide appropriate treatment strategies [27]. When used carefully and in combination with other imaging modalities, they can aid in early detection, assessment of treatment response, and personalized treatment planning. However, it is worth noting that PET and SPECT also have some limitations: relatively expensive imaging and potential exposure to ionizing radiation due to the use of radioactive tracers.

5. Ultrasound

Ultrasound imaging, also known as sonography, utilizes high-frequency sound waves to create real-time images or video of soft tissues inside the body. It is a rapid, low-cost, and widely available imaging tool that has the advantage of not exposing patients to ionizing radiation, making it particularly important in pediatrics. Ultrasound is commonly used for diagnosing diseases and assessing their structure and functionality [24]. Gas-filled microbubbles can serve as contrast agents in ultrasound imaging, enhancing the visualization of disease processes such as tumors or areas of inflammation by undergoing acoustic oscillations or collapsing at the target site, resulting in the generation of strong echoes or signals [28]. However, ultrasound has inherent limitations in terms of sensitivity and depth of penetration, which may impact its diagnostic accuracy in certain cases. In such situations, magnetic resonance imaging (MRI) may be preferred over ultrasound due to its higher diagnostic accuracy, making it a more reliable imaging modality [29].

6. Photoacoustic Tomography

Photoacoustic tomography (PAT) is a cutting-edge imaging technique that combines ultrasound and laser-induced photoacoustic signals to generate detailed images of biological tissues, including the GI tract, with high contrast in optical imaging and high resolution in deep tissues with acoustic imaging ^[30][31][32][30,31,32]. PAT uses laser pulses to create photoacoustic waves that are generated when absorbed light is converted into heat, leading to localized thermoelastic expansion and subsequent ultrasound waves, then detected by ultrasonic sensors, which are then analyzed to produce images. PAT is essentially optical imaging, good acoustic spatial resolution can be achieved even at imaging depths of 5–6 cm, making it suitable for imaging deeper structures in the GI tract ^[11][33][11,33]. PAT has high sensitivity and can detect molecular-level changes in tissues, making it a promising tool for clinical images, such as tumor diagnosis imaging ^[34][35][34,35], whole-body imaging of small animals [36], and various other medical applications [37].