Multimodality Diagnosis of Mesenteric Ischemia

Summary

This article presents a multimodal approach that aims to overcome the limitations of traditional methods in detecting mesenteric ischemia and preventing bowel necrosis. The presented technique offers a promising solution by combining state-of-the-art ultrasonography with cutting-edge near-infrared light technologies.

Abstract

Early diagnosis of mesenteric ischemia remains challenging because mesenteric ischemia presents with no key symptoms or physical findings, and no laboratory data specifically indicates intestinal tissue ischemic status before necrosis develops. While computed tomography is the standard for diagnostic imaging, there are several limitations: (1) repeated assessments are associated with increased radiation exposure and risk of renal damage; (2) the computed tomography findings can be misleading because necrosis occasionally occurs despite opacified mesenteric arteries; and (3) computed tomography is not necessarily available within the golden time of salvaging the intestines for those patients in the operating room or at a place far from the hospital. This article describes a challenge to overcome such limitations using ultrasonography and near-infrared light, including clinical studies. The former is capable of providing not only morphologic and kinetic information of the intestines but also perfusion of the mesenteric vessels in real-time without transferring the patient or exposing them to radiation. Transesophageal echocardiography enables precise assessment of mesenteric perfusion in the OR, ER, or ICU. Representative findings of mesenteric ischemia in seven aortic dissection cases are presented. Near-infrared imaging with indocyanine green helps visualize the perfusion of vessels and intestinal tissues although this application requires laparotomy. Findings in two cases (aortic aneurysm) are shown. Near-infrared spectroscopy demonstrates oxygen debt in the intestinal tissue as digital data and can be a candidate for early detection of mesenteric ischemia without laparotomy. The accuracy of these assessments has been confirmed by intraoperative inspections and postoperative course (prognosis).

Introduction

Acute mesenteric ischemia can be life-threatening unless diagnosed and treated without delay^1,2; however, early diagnosis followed by restoration of perfusion before progressing to bowel necrosis, preferably within 4 h, remains challenging for several reasons: (1) mesenteric ischemia is caused via multiple mechanisms and associated with several diseases managed by different specialties; (2) there are no symptoms, signs, or laboratory data specific for mesenteric ischemia; and (3) computed tomography (CT), the gold standard for diagnostic imaging, is misleading because ischemia can be present despite an opacified superior mesenteric artery (SMA)^2,3,4,5.

Causes of mesenteric ischemia include embolism, thrombosis, dissection, or non-occlusive mesenteric ischemia (NOMI)^3,6. Embolism is caused by a cardiogenic thrombus in patients with atrial fibrillation, dilated left ventricle, or atheroma in the aorta, which is asymptomatic until embolization. Occasionally, a thrombus is generated in the SMA or superior mesenteric vein. It has recently been shown that COVID-19 can lead to thrombus formation⁷. In aortic dissection, the intimal flap in the aorta occludes the orifice of the SMA, or dissection extends into the SMA, and an expanded false lumen compresses the true lumen. Because this obstruction is "dynamic," mesenteric ischemia occurs even when the SMA is shown to be opacified on contrast CT. It is not uncommon for mesenteric ischemia to appear together with other critical conditions, such as stroke, myocardial infarction, or aortic rupture, thus necessitating a prompt and accurate diagnosis to prioritize treatment. In patients who undergo blood dialysis for years, the SMA is often narrowed due to calcifications, and the blood flow can be critically reduced following cardiac surgery using extracorporeal circulation or various types of stress^8,9,10. NOMI can be caused by inadequate oxygen supply to the SMA due to heart failure, cardiac arrest, or hypoxemia despite a patent SMA^11,12,13. Considering various etiologies and patterns of occurrence, not only blood flow in the SMA but also ischemic status in the intestinal wall must be assessed.

Another reason for delayed diagnosis is a lack of key symptoms or physical findings. Defense becomes obvious after the intestine is necrotized. Although several laboratory tests, such as C-reactive protein, lactate, citrulline, or intestinal fatty acid-binding protein, have been investigated as potential indicators of mesenteric ischemia^4,14, no laboratory test has been shown to detect an early stage of mesenteric ischemia to date¹⁵. Although CT is the standard diagnostic imaging modality of mesenteric ischemia^16,17,18, there can be errors in diagnosis or pitfalls in the filming technique^5,19, and thus expertise is needed for an accurate diagnosis, which may necessitate the transfer of the patient to another facility. In addition, CT is not available for patients in the operating room (OR), emergency department (ER), or intensive care unit (ICU) who cannot be transferred to the Radiology Department. Allergies to contrast media, renal toxicity, or radiation exposure also limit CT as the initial diagnostic examination for every patient with abdominal pain.

Bowel ischemia is also problematic for plastic and reconstructive surgeons. During radical surgery for pharyngeal cancer, a free jejunal flap is used to reconstruct the resected pharynx. A portion of the jejunum is harvested with an artery and vein pedicle, which is anastomosed to the vessels in the cervical region, followed by anastomosis of the jejunal flap to the pharynx and esophagus. To confirm the competency of the vascular anastomosis, indocyanine (ICG) imaging was performed intraoperatively (sections 3). However, there are occasions when the flap develops necrosis within several days after surgery. Although rare, flap necrosis can be fatal unless detected and treated without delay. Thus, various attempts for detecting jejunal ischemia have been developed, such as frequent ultrasonography (US) to confirm blood flow, repeated endoscopy to verify mucosal color, or designating a sentinel portion of the jejunum to monitor perfusion, which is buried afterward by an additional surgical procedure^20,21,22; however, such maneuvers are difficult for both patients and physicians. Other modalities applied to the clinical use for diagnosing bowel ischemia include optical coherence tomography²³, laser speckle contrast imaging²⁴, sidestream dark field imaging²⁵, and incident dark field imaging²⁶. These promising modalities are expected to become widely available through further development.

Considering the nature of mesenteric ischemia, which affects several fields in various situations, it is important to have multiple measures for detecting it. This article proposes two potential candidates for this purpose, US and near-infrared light and presents the representative findings.

Protocol

A clinical investigation of ICG imaging was performed under approval by the Ethics Committee of Kochi Medical School with informed consent from every patient. A total of 25 patients were included, who underwent reconstructive surgery using free jejunal graft following resection of cancer of the pharynx or cervical esophagus between 2011 and 2016. Regarding the US, the video records obtained in clinical practice between 2000 and 2018 have been reviewed. Ethical approval was waived on this, according to the institutional ethical review committee.

1. Transesophageal echocardiography (TEE)

NOTE: TEE, which necessitates the insertion of an esophageal probe, is suitable for making a diagnosis or monitoring in the OR or ICU where CT assessment is not available. TEE provides morphologic and kinetic information as well as the perfusion status of the intestine^27,28. Although it requires expertise in visualizing the SMA, it is not so hard for experienced heart and thoracic aorta examiners. The SMA can be visualized with the TEE probe (see Table of Materials) advanced into the stomach and the transducer directed posteriorly (Figure 1A).

1. Visualize the descending aorta on the short axis (scanning plane 0°), then advance the probe into the stomach with the image of the aorta kept in view by rotating the probe counterclockwise with a slight anteflexion of the probe tip to keep the transducer in contact with the esophageal wall.
2. If the image of the aorta moves downward, bend the probe tip further (Figure 1B).
3. Use color Doppler mode to facilitate the identification of visceral branches by flow signal, and ensure that the orifice of the celiac artery appears at the 12 o'clock position of the abdominal aorta (Figure 1C). It divides into two or three arteries within a few centimeters of the orifice.
4. Advance the probe one inch further so that the SMA appears at the 12-2 o'clock position.
   NOTE: A leftward bending of the probe tip is helpful to rotate the image and depict the SMA at 12 o'clock position.
5. Ensure that the distal portion of the SMA is located between the pancreas (splenic vein) and abdominal aorta, where the left renal vein crosses behind the SMA.
6. Rotate the scanning plane to 90° to visualize the long-axis view of the aorta and visceral branches. The distal portion of the SMA can be assessed more easily (Figure 1D).
   NOTE: Figure 1C,D show the TEE findings in a cardiovascular surgical case without mesenteric ischemia.

2. Abdominal US

NOTE: This modality is suitable for suspecting or excluding mesenteric ischemia among several patients with abdominal pain, together with physical examination. It is used for assessing the morphology and kinetics of the intestine and the blood flow in the SMA. Figure 2A shows the place of the probe (see Table of Materials) for each purpose.

1. Use a convex or sector probe with a frequency range of 2 to 5 MHz to facilitate visualization and above assessment of the intestine via the abdominal wall with adequate resolution and sensitivity.
   NOTE: Use a transducer with a frequency range between 2.5 and 5 MHz for visualizing the bowels in the abdomen with the gain setting maximal without generating background noise.
2. Place the probe on the abdominal wall around the navel to visualize the intestine (Figure 2B). Find any acoustic window (yellow arrow) between the intestinal gas (blue dotted line).
3. Check the size and peristaltic movement of the intestine, mucosal edema, or the presence of ascites around it. The latter indicates that intestinal necrosis takes place.
4. For assessing the SMA flow, the probe was placed vertically above the navel level. Find the SMA, which arises from the abdominal aorta and directs caudally within a few centimeters (Figure 2C).
   ​NOTE: The US findings in Figure 2B,C was recorded in healthy individuals.

3. ICG imaging

NOTE: This modality is suitable for assessing the perfusion of the tissues in the surgical field.

1. Prepare the ICG imaging system following the manufacturer's instructions (see Table of Materials).
2. Inject a total of 2.5 mg ICG (see Table of Materials) dissolved in 10 mL of distilled water (0.25 mg/mL) into the central venous line, followed by flushing with 10 mL of saline (Figure 3A).
3. Visualize the perfused ICG into the mesenteric artery and then the intestinal tissue on display (Figure 3B). It usually appears approximately 10 to 20 s after injection.
   ​NOTE: The ICG imaging findings in Figure 3B were recorded in a reconstruction case with a free jejunal graft enrolled in the above study.

4. Near-infrared spectroscopy (NIRS)

NOTE: To solve the problem in plastic and reconstructive surgery (as mentioned in the Introduction section), this study proposed the use of the NIRS system, which has been used in cardiovascular surgery²⁹; however, validation to confirm that rSO₂ reflects the ischemic status of the jejunum was needed. When the jejunal flap was harvested, an NIRS sensor was placed on the jejunum, and changes in rSO₂ were monitored when the artery and vein were clamped, and perfusion was resumed after reconstruction. In addition, rSO₂ changes were observed for 3 days postoperatively with the NIRS sensor placed on the skin of the neck. The recommended procedures for assessing the rSO₂ of the intestine directly in the surgical field are described here.

1. Prepare the NIRS system following the manufacturer's instructions (see Table of Materials) (Figure 4A).
2. Use an appropriate sensor for measuring the rSO₂ of the tissue according to the depth of the target region to be assessed (Figure 4B). Place the sensor directly on it with light contact so as not to press excessively.
   NOTE: This study used a sensor with a distance between the emitter and receiver of 2 cm.
3. Check the rSO₂ value indicated on display, updated every 5 s (Figure 4B).

Results

TEE
There were two types of findings: (1) "branch type" with a true compressed lumen in the SMA by an expanded false lumen without blood flow, and (2) "aortic type" with the intimal flap at the orifice of the SMA and lack of blood flow in the SMA (Figure 5A). The representative TEE findings of three cases with bowel necrosis caused by acute aortic dissection are shown. In one case of the former type, the true lumen in the SMA were severely compressed (<...

Discussion

Mesenteric ischemia remains an unsolved problem beyond the clinical field. To solve such a common problem, similar pathology in other organs may be helpful to take a hint. The concept of "ischemic cascade" was proposed for acute myocardial infarction³², and regional wall motion abnormalities (hypokinesis, akinesis, and dyskinesis) located at the early stage of the cascade have been used as an indicator of myocardial infarction instead of coronary blood flow, which cannot be assessed noninv...

Materials

Name	Company	Catalog Number	Comments
HyperEye Medical System	Mizuho Ikakogyo Co., Ltd.		ICG imaging system used in Figure 3
Indocyanine green	Daiichi Sankyo Co., Ltd.		ICG used for ICG imaging in Figure 3
TEE system	Philips Electronics	iE33	TEE system used in Figure 5
TOS-96, TOS-OR	TOSTEC Co.		NIRS system used in Figure 4
Ultrasonographic system	Hitachi, Co.	EUB-555, EUP-ES322	echo system used in Figure 1
Ultrasonographic system	Aloka Co.	SSD 5500	echo system used in Figure 2
Vscan	GE Healthcare Co.		Palm-sized echo used in Figure 2