A Study Comparing Transperineal Ultrasound, Magnetic Resonance Imaging, Endoscopic Ultrasound, and Examination Under Anesthesia to Detect and Classify Perianal Fistulas in Patients With Crohn's Disease or Fistulas of Unknown Cause (TRANSIT CD)

Perianal fistulas are a challenging and often debilitating complication of anorectal and inflammatory bowel diseases, particularly Crohn's disease. Up to 40% of people with Crohn's disease may develop perianal fistulas during the course of their illness. These fistulas are frequently complex, may recur, and can severely affect quality of life. They are associated with symptoms such as discharge, swelling, pain, infection, and, in some cases, incontinence or systemic sepsis. Accurate diagnosis and anatomical characterization of these fistulas are essential for determining the most effective medical and surgical treatment strategies.

Traditional imaging strategies include Magnetic Resonance Imaging (MRI), which is currently considered the non-invasive standard for anatomical delineation, and Examination Under Anesthesia (EUA), which serves as the gold standard due to the ability to directly examine the anatomy and intervene surgically if necessary. However, both methods have limitations. MRI is costly, may not be readily available in resource-limited settings, and is not suitable for all patients (e.g., those with certain implants or claustrophobia). EUA is invasive, requires anesthesia, and may not be feasible for repeated use in follow-up or outpatient care.

Alternative imaging modalities such as Transperineal Ultrasound (TPUS) and Endoscopic Ultrasound (EUS) are being explored for their diagnostic utility. TPUS is a non-invasive, low-cost, real-time modality that can be performed at the bedside or in outpatient settings. EUS, while more invasive, offers high-resolution images of the anal canal and surrounding structures and is increasingly used for evaluating anorectal diseases.

The TRANSIT-CD study (A Quadrimodal Comparison of TRAnsperiNeal and MR-based Sonographic Investigation with Integrated Testing using Endoscopic Ultrasound and Examination Under Anesthesia) is a prospective, single-center, diagnostic accuracy study designed to compare the performance of four imaging modalities-TPUS, MRI, EUS, and EUA-in evaluating perianal fistulas in people with Crohn's disease and cryptogenic (non-Crohn's) fistulas.

Study Design and Objectives The study will enroll adults aged 18 to 75 years with a clinical diagnosis or suspicion of perianal fistula. Each participant will undergo four imaging tests-TPUS, MRI, EUS, and EUA-within a maximum interval of 10 days. The order of testing is predefined and all interpretations will be performed independently by blinded experts in each modality.

The primary objective is to compare the per-lesion sensitivity of TPUS and MRI for detecting perianal fistulas, using EUS as the reference standard and EUA as the gold standard.

Secondary objectives include:

Comparing TPUS and MRI for detecting internal openings and perianal abscesses Evaluating classification accuracy using Parks classification and American Gastroenterological Association (AGA) criteria (simple vs. complex fistulas) Determining whether findings from TPUS and MRI result in a change in clinical management

Exploratory objectives include:

Assessing diagnostic accuracy by disease type (Crohn's vs. cryptogenic) Comparing modality performance in high (above the levator ani muscle) vs. low fistulas Evaluating inter-modality agreement and confidence levels of reporting physicians Methodology

Transperineal Ultrasound (TPUS) Performed by an expert radiologist using a high-end ultrasound platform with microconvex and high-frequency linear probes. The patient is positioned in the left lateral decubitus position. Both axial and sagittal images are obtained. Parameters assessed include tract presence, type, internal openings, secondary extensions, and associated abscesses.

Magnetic Resonance Imaging (MRI) Conducted using a 1.5 Tesla MRI scanner with T2-weighted, STIR, and post-contrast T1-weighted fat-suppressed sequences in axial, sagittal, and coronal planes. MRI findings are independently interpreted by radiologists blinded to TPUS and EUS findings. Fistulas are characterized using standard classification systems and the presence of abscesses and internal openings is documented.

Endoscopic Ultrasound (EUS) EUS is performed using a linear echoendoscope and dedicated EUS processor. The procedure does not require bowel preparation. A 360-degree evaluation of the anal canal and surrounding structures is performed to detect fistulous tracts, internal openings, and collections. EUS serves as the reference standard for diagnostic comparison.

Examination Under Anesthesia (EUA) EUA is performed by an experienced colorectal surgeon under spinal or general anesthesia. This procedure allows direct probing of the fistula tract, identification of internal openings, and classification of the fistula using tactile and visual assessment. EUA is considered the gold standard in this study.

Each modality's findings are documented in structured case report forms. The findings include:

Fistula presence and number Parks classification and AGA complexity score Internal and external openings Abscess presence and dimensions Secondary tracts Confidence scores All data are recorded per lesion, per patient.

Blinding and Data Integrity All imaging studies will be interpreted independently by modality-specific experts, who are blinded to the findings of other modalities. Discrepant findings will be resolved through consensus by the principal investigators. A secure electronic database will be used for data capture, ensuring patient confidentiality and auditability.

Clinical Impact Assessment The study will also track whether imaging findings lead to a change in management plans (e.g., additional imaging, medical therapy, surgical planning). These decisions will be documented by treating clinicians based on the initial and subsequent imaging findings.

Sample Size and Statistical Analysis

This pilot study aims to recruit approximately 100 participants. Based on previous literature (Maconi et al., 2017), the study is powered to detect a difference in diagnostic sensitivity between TPUS and MRI. The analysis includes:

Calculation of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) McNemar's test for paired comparisons Cohen's kappa for inter-modality agreement Receiver Operating Characteristic (ROC) curve analysis Subgroup analyses by diagnosis type and fistula location

Significance This is the first prospective study to compare all four major imaging modalities in the same patient cohort with suspected or confirmed perianal fistulas. By benchmarking TPUS and MRI against both EUS and EUA, the TRANSIT-CD study provides a robust framework for evaluating diagnostic accuracy and impact on care. The results may support broader use of TPUS as a first-line diagnostic tool, particularly in outpatient and low-resource settings where access to MRI or EUA is limited. It may also help refine imaging protocols for complex perianal Crohn's disease.

Ethical Considerations All imaging procedures in this study are part of routine clinical care. No experimental treatments are being tested. The study has been approved by the Institutional Ethics Committee and informed consent will be obtained from all participants. There are no additional risks introduced beyond standard diagnostic procedures. All data will be anonymized and securely stored.