Comparison of Tc-99 m scintigraphic method and radiological method for colon transmit assessment in patients with functional constipation

Abstract

Background

The methods for assessing colonic transit in patients with functional constipation include the radiological method and Tc-99m scintigraphic method. This study aims to validate the practicality and accuracy of the Tc-99m scintigraphic method in evaluating colon transit, while also exploring the significance of the geometric center (GC).

Methods

Our study is a single-center, retrospective analysis. We examined the medical records of 47 patients, who underwent colonic transit by the Tc-99m scintigraphic method and the radiological method for investigation of chronic constipation. Geometric center (GC) and transmit index (TI) were calculated respectively in these two methods. The patients were divided into four types of constipation: normal transit constipation (NTC), slow transit constipation (STC), defecatory disorders (DD) and STC combined with DD.

Results

The results of the Tc-99m scintigraphic method and radiological method were consistent in the diagnosis of slow colon transmission (Kappa value = 0.718, P < 0.001). TI and 48-h GC were positively correlated (r = 0.657, p = 0.001). Patients with DD exhibited higher 24-h GC and 48-h GC values compared to those with STC.

Conclusion

Tc-99m scintigraphic method can be used to evaluate colonic transit in patients with constipation, and GC values may be used to distinguish the types of constipation.

Background

Chronic constipation, a widespread yet frequently underestimated gastrointestinal disorder, affects a considerable proportion of the global population, with prevalence estimates ranging from 10 to 15% worldwide [1]. A systematic review, which included 45 studies with 275,260 participants, found that the pooled prevalence of functional constipation was 10.1% using the Rome IV criteria [2]. This condition significantly impacts patients' quality of life and burdens healthcare systems. The majority of constipation cases in the population are attributed to functional constipation (FC), which lacks an organic cause and falls under the category of functional gastrointestinal disease. After the clinical assessment, functional constipation patients can be classified into the following subtypes: (1) normal transit constipation (NTC), (2) slow transit constipation (STC), (3) defecatory disorders (DD), and (4) STC and DD [3, 4].

These normal transit constipation (NTC) patients show neither slow transit constipation nor anorectal dysfunction; only self-reported constipation symptoms exist [3]. The exact pathophysiology underlying this subtype remains unclear. Slow-transit constipation (STC) is characterized by loss of interstitial cells of Cajal and autonomic denervation, which leads to a reduction in overall colonic motility. The delayed stool movement through the colon leads to water absorption, stool hardening, and subsequent evacuation difficulties [5–7]. The first-line therapy of STC combines polyethylene glycol, prokinetic agents (prucalopride, linaclotide), and, in refractory cases, laparoscopic subtotal colectomy [8]. Defecatory disorders (DD) arise from paradoxical puborectalis contraction and incomplete rectal evacuation; treatment centres on biofeedback training to correct coordination, supplemented with laxatives [4]. Overlap between defecatory disorders (DD) and slow transit constipation (STC) has been reported; these patients exhibit both colonic inertia and outlet obstruction.

The thorough assessment of colonic transit is indispensable for diagnosing FC, defining its pathophysiologic subtype, and tailoring individualized therapeutic strategies. Current measurement methods of colonic transit primarily include the radiopaque marker test, wireless power capsule, and colon scintigraphy [9]. The radiopaque marker test represents the most economical and simplest method for assessing colonic transit and is widely used in China. However, patients are exposed to radiation, and the radiopaque markers differ from normal food, potentially affecting the assessment's accuracy. The wireless power capsule is devoid of radiation but requires expensive technical equipment, limiting its widespread use. Colon scintigraphy involves mixing a radionuclide with food and allowing it to enter the intestine, thereby best reflecting the physiological state and outlining the colon [10].

The 2 radioisotopes most commonly used for colon scintigraphy are Tc-99 m and In-111. Tc-99 m has a short half-life (about 6 h) and can be used to evaluate small bowel transit, whereas In-111 has a long half-life (about 67 h) and can be employed in colon transit studies. Whole gut transit scintigraphy usually uses a standard solid (Tc-99 m egg sandwich)—liquid (In-111 water) meal [10]. In China, only Tc-99 m is available. In clinical practice, we observed that using only the solid (Tc-99 m egg sandwich) meal in most constipation patients can also make colon imaging at 24 and 48 h, and the residual radioactivity can be quantitatively calculated. This may be because slow colonic transit or accumulation of stool leads to radionuclide accumulation, which partially mitigates nuclide attenuation. Therefore, we hypothesize that scintigraphy using Tc-99 m may have a certain value in assessing colonic transit in FC patients.

The study aims to explore the utility of the Tc-99 m scintigraphic method in assessing colonic transit and provide better and more diverse objective examination methods for the clinical evaluation of FC.

Method

Subjects

The flowchart of the research is as Fig. 1. We retrospectively included patients who visited the constipation clinic of our Hospital from January 2018 to February 2024 and met the following inclusion criteria.

Fig. 1.

Flowchart of the research

Inclusion criteria:

1. Aged ≥18 years;

2. Meet the Rome IV diagnostic criteria for functional constipation;

3. Completed Tc-99m scintigraphic method and radiopaque marker test; Tc-99m scintigraphic method: using the 5mCi Tc-99m-DTPA labeled solid meal, taking images at 2, 4, 6, 24, 48, and 72 hours

Exclusion criteria:

1. Have clear anatomical abnormalities or skeletal deformities or congenital intestinal diseases;

2. Constipation caused by drugs or organic causes;

3. Severe organ dysfunction or disease with a life expectancy of less than 3 months.

The study was approved by the Ethics Committee.

Radiopaque marker test

We implemented the radiopaque marker test based on the “Hinton technique” [11]. The patients consumed a capsule with 24 radiopaque markers inside on the first day. A plain abdominal radiograph was obtained respectively on days 3 and 4. Patients maintained their regular diet and social routines but refrained from using laxatives, enemas, or bulking agents throughout the duration. Calculate the residual rate as residual marker number/24 × 100%, a rate of residual more than 20% on day 4 is considered to be a slow colonic transit. A line was drawn from the thoracic spinous process to the L5 spinous process, and then a tangent line was drawn from the L5 spinous process to the right pelvic outlet and left iliac crest, serving as landmarks delineated the areas of the right, left, and rectosigmoid colon (Fig. 2) [12]. The colon transit index (TI) was determined by dividing the count of rectum sigmoid colon marker remnants by the total count of marker remnants in the entire colon. The closer the TI value is to 0, the more likely it is STC; the closer the TI value is to 1, the more likely it is DD.

Fig. 2.

Division of the colonic region, R: the right colon region, L: the left colon region, RS: the sigmoid colon and rectum region

Tc-99 m scintigraphic method

The solid meal includes 5 mCi Tc-99 m-DTPA labeled egg white (120 g) and 2 slices of white bread (120 kcal) [10]. Images were acquired in the upright posture from front and back scans using a gamma scintillation camera (GE Discovery 670). The images were gathered at 2, 4, 6, 24, 48, and 72 h (Fig. 3). Radionuclide decay was adjusted, and the colon was marked by combining sequential scans. For each subject, regions of interest (ROI) were determined and drawn in the following manner: ROI 1, caecum and ascending colon including the hepatic flexure; ROI 2, transverse colon including the splenic flexure; ROI 3, descending colon; ROI 4, sigmoid colon and rectum; ROI 5, stool (Fig. 4). The geometric center (GC) is determined by summing the weighted fractions, which are represented by the counts in each region multiplied by the region number and then divided by the total counts. It is similar to the center of mass of the distributed activity in the colon, and it quantitatively tracks the advancement of radiolabeled stool as it traverses the colon [10]. We calculated GC in 24 h and 48 h respectively. The calculation formula for the GC value is as follows [13]:

Fig. 3.

The images collected through the Tc-99 m scintigraphic method

Fig. 4.

Division of ROI and calculation of GC. In this patient, the total Tc-99 m counts of abdomen = 8434, counts in ROI1 = 1859, counts in ROI2 = 1885, counts in ROI3 = 3789, counts in ROI4 = 901, counts in ROI5 = 0 (The patient has not defecated), GC = (1859 × 1 + 1885 × 2 + 3789 × 3 + 901 × 4)/8434 = 2.44. ROI: Region of Interest GC: Geometric Center

Statistical methods

Non-parametric methods were applied. Differences among groups were assessed using the Kruskal–Wallis test. The connection between the GC and TI was assessed using Spearman's rank correlation coefficient. Kappa consistency test was used to compare the radiological and the scintigraphic method with respect to prolonged or normal transit time. A P-value below 0.05 was considered as significant. SPSS software was used for the calculations.

Results

Patient characteristics

From 2018 to 2024, a total number of 52 constipated patients participated in both the radiopaque marker test and colonic transit scintigraphy. Following the removal of patients with megacolon (n = 1) and those with incomplete or suboptimal study data (n = 4), 47 patients (30 female and 17 male) were ultimately enrolled in the research, with an average age of 49.6 ± 17.5 (mean ± SD) years. Based on the radiopaque marker test and anorectal manometry results, we divided constipation patients into four types: NTC, STC, DD, and STC combined with DD. Constipation type: STC 9 cases (18.8%), DD 17 cases (35.4%), STC + DD 18 cases (37.5%), NTC 3 cases (6.3%). Patient demographics are shown in Table 1.

Table 1.

Patient demographics: all patients and by colon transit pattern

Category	All	NTC	STC	DD	STC combined with DD
Total(n)	47	3	9	17	18
Age(average)	49.6	59.7	58.0	54.8	38.8
Gender(%Female)	63.8%	100%	44.4%	52.9%	77.8%
Duration of constipation(years)	10.3	29.3	7.0	9.4	9.9

The Tc-99 m scintigraphic method can successfully perform colonic imaging

Although the half-life of Tc-99 m is only 6 h, our experience shows that even in constipated patients with normal transit, the colon can still be visualized at 24- and 48-h using Tc-99 m labeled solid meal (Fig. 5). Probably because the accumulation of stool leads to radionuclide accumulation, which partially mitigates nuclide attenuation. This characteristic allows for the acquisition of colon images at 24-h and 48-h. By analyzing these images, clinicians can identify areas of radionuclide accumulation and determine the extent of slow transit.

Fig. 5.

The images collected through the 99mTc scintigraphic method in NTC patient

The agreement between the Tc-99 m scintigraphic method and the radiopaque marker test

According to the radiopaque marker test, 33 patients were identified with slow colonic transit, while 14 patients had normal transit. Conversely, the radionuclide method categorized 29 patients as having slow colonic transit and 18 as normal (Table 2). A comparison of the results from both methods revealed that 41 patients had consistent findings between the radiopaque marker test and the radionuclide method. The Kappa (κ) coefficient of concordance was calculated to quantify the agreement between these two methods. The resulting Kappa value was 0.718, with a P-value less than 0.001. This statistical outcome indicates good agreement between the radiopaque marker test and the radionuclide method in assessing colonic transit.

Table 2.

Comparison between the results of Radiopaque Marker Test and Tc-99 m Scintigraphic Method

Tc-99 m Scintigraphic Method	Radiopaque Marker Test(n)		Total (n)
	Slow Transmit	Normal transmit
Slow Transmit	28	1	29
Normal transmit	5	13	18
Total(n)	33	14	47

Geometric center (GC) is positively correlated with colonic transport index (TI)

For the scintigraphic method, the geometric center (GC) is calculated for quantifying colon transit. In patients with abnormal colonic transit, the larger the GC, which means that the nuclide accumulates in the lower intestine, the more prone to defecatory disorders. In the radiopaque marker test, the transmit index (TI) quantitatively evaluated colonic transmission. The closer TI is to 1, the more likely it is to defecatory disorders, and the closer TI is to 0, the more likely it is to slow transit constipation.

We further investigated the correlation between geometric center (GC) and transmit index (TI). The 48 h TI of patients with the slow transmission of the radiopaque marker test was summarized, as shown in Fig. 6. 48hGC and 48hTI were positively correlated (r = 0.657, p = 0.001), indicating a moderate correlation (see Fig. 7).

Fig. 6.

The 48 h TI of patients with the slow transmission of the Radiopaque Marker Test, TI: Transmit Index

Fig. 7.

The correlation between geometric center (GC) and transmit

Association of GC with constipation types

The results indicate differences in GC (Table 3). Specifically, patients with defecatory disorders (DD) exhibited higher 24-h GC and 48-h GC values compared to those with slow transit constipation (STC), and these differences were statistically significant (Fig. 8). Furthermore, the 48-h GC values of patients with DD were notably higher than those of patients with STC + DD. Conversely, no statistically significant difference was observed between patients with STC and those with STC + DD, potentially suggesting overlapping mechanisms between these two types. These findings hint at the necessity of conducting further research with a larger sample size, which might lead to the establishment of reference ranges for 48-h GC values that could aid in differentiating constipation subtypes.

Table 3.

The geometric center (GC) of different constipation types

	STC	STC + DD	DD	NTC
	M ± SD	M ± SD	M ± SD	M ± SD
24hGC	1.57 ± 0.29	2.09 ± 0.74	2.76 ± 1.09	4.17 ± 0.73
48hGC	2.15 ± 0.54	2.61 ± 0.59	4.22 ± 0.89	4.34 ± 0.36

Fig. 8.

The geometric center (GC) among patients with different types of constipation

Conclusion

This study verified the clinical feasibility and reliability of Tc-99 m colonic transit scintigraphy in the diagnosis of chronic constipation. Firstly, in all the patients, the tracer remained visible within 48 h, which may indicate that fecal accumulation weakened the physical decay of Tc-99 m in patients with constipation. This observation eliminates the traditional concern about the 6-h half-life and validates that the Tc-99 m scintigraphic method can successfully perform colonic imaging. Secondly, the comparison with the radiopaque marker test (still regarded as the de facto reference) showed good consistency (κ = 0.718, p < 0.001), which indicates that the Tc-99 m scintigraphic method can safely replace or supplement the radiopaque marker test without losing diagnostic accuracy, while sparing patients from multiple X-ray films.

Thirdly, the quantitative parameters obtained by the two methods are consistent with each other. The 48-h geometric center (GC) and the 48-h transit index (TI) are positively correlated (r = 0.657, p = 0.001). More importantly, GC distinguishes clinically relevant phenotypes: patients with defecatory disorders (DD) exhibited notably higher 48-h GC values compared to those with STC and STC + DD. This indicates the possibility of using 48hGC to define the subtypes of constipation.

In conclusion, Tc-99 m scintigraphy offers a single isotope-labeled quantitative examination as an alternative or supplement to traditional examination methods.

Discussion

The results of the Tc-99 m scintigraphic method is in accordance with the result of classical radiological method

The main innovation of this study lies in clarifying that even without the application of In-111, radionuclide imaging using Tc-99 m alone is feasible for assessing colon transit in patients with functional constipation. This non-invasive imaging technique offers a novel perspective on evaluating gastrointestinal motility, particularly in constipation, where traditional diagnostic methods may have limitations. Our findings demonstrate a moderate correlation between the results obtained via the Tc-99 m scintigraphic method and the classical radiological method, suggesting that the scintigraphic approach can serve as a viable alternative or complementary tool in the clinical assessment of colon transit.

Potential Utility of 48-h GC in Differentiating Constipation Types

Another intriguing aspect of our study is the exploration of the 48-h GC as a potential marker for differentiating various types of constipation. While this study did not directly categorize or analyze specific constipation subtypes, the notion that GC might offer insights into constipation heterogeneity deserves further investigation. By measuring the geometric center, Tc-99 m scintigraphy may help identify distinct patterns of colon transit that could correlate with different constipation phenotypes. Such distinctions could be crucial for tailoring therapeutic strategies and improving patient outcomes, as the management of constipation often requires a nuanced approach based on its underlying cause and presentation.

Limitations

Despite these promising findings, our study is not without limitations. The SNMMI and EANM Practice Guideline introduced a complete colonic transit study as including images and GC calculation at 24, 48, and 72 h. However, limited by the half-life of the Tc-99 m, we can't achieve a 72-h GC and use 72-h GC values to compare with radiological methods. Therefore, our data cannot be benchmarked directly against the normative ranges published in the guideline. Besides, a “central” GC at 48 h may hide a recto-sigmoid accumulation that would have become obvious between 48 and 72 h; thus, DD may be misclassified as normal. We explicitly state that our study is limited to 48-h imaging. And in future studies, we will try to adjust the diagnostic thresholds in our pilot data instead of the guideline cut-off to retain > 90% specificity. In addition, this study is a single-center research with a relatively small sample size, and the distribution of constipation patients in our sample is not uniform. To address these limitations, future research should aim to conduct multicenter trials with larger and more diverse patient populations, ensuring a balanced representation of different constipation types and severities. Furthermore, incorporating additional diagnostic tools and patient-reported outcome measures could provide a more holistic view of colon transit and its impact on patient's quality of life, ultimately contributing to more personalized and effective treatment strategies for functional constipation.

Abbreviations

FC

Functional Constipation

NTC

Normal Transit Constipation

STC

Slow Transit Constipation

DD

Defecatory Disorders

ROI

Region of Interest

GC

Geometric Center

TI

Transmit Index

Tc-99m

Technetium-99m

Tc-99m-DTPA

Technetium-99m Diethylenetriaminepentaacetic Acid

Authors’ contributions

Y.T. wrote the main manuscript text. Y. L. prepared the data curation and formal analysis. T.Y. and Q.W. prepared the data curation. X.J. and Z. H. contributed to the conceptualization and supervision. All authors reviewed the manuscript.

Funding

No financial support was received for the preparation of the manuscript.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

This retrospective study was conducted in accordance with the ethical principles of the Declaration of Helsinki. The study did not involve any additional interventions on patients and the analyzed data did not include patients' personal information. Therefore, the requirement for informed consent from participants was waived. The Ethics Committee of the Beijing Tsinghua Changgung Hospital has approved this study (ethics approval number 25046–4-01). The study strictly protected patients' rights and welfare, ensuring that all research activities complied with the ethical guidelines outlined in the Declaration of Helsinki.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.