Intranodal dynamic contrast-enhanced CT lymphangiography and dynamic contrast-enhanced MR lymphangiography in microminipig.

OBJECTIVES: To evaluate the feasibility and image quality of intranodal dynamic contrast-enhanced CT lymphangiography (DCCTL) and dynamic contrast-enhanced MR lymphangiography (DCMRL) in microminipigs. METHODS: Our institution's committee for animal research and welfare provided approval. Three microminipigs underwent DCCTL and DCMRL after inguinal lymph node injection of 0.1 mL/kg contrast media. Mean CT values on DCCTL and signal intensity (SI) on DCMRL were measured at the venous angle and thoracic duct (TD). The contrast enhancement index (CEI; increase in CT values pre- to post-contrast) and signal intensity ratio (SIR; SI of lymph divided by SI of muscle) were evaluated. The morphologic legibility, visibility, and continuity of lymphatics were qualitatively evaluated using a 4-point scale. Two microminipigs underwent DCCTL and DCMRL after lymphatic disruption and the detectability of lymphatic leakage was evaluated. RESULTS: The CEI peaked at 5-10 min in all microminipigs. The SIR peaked at 2-4 min in two microminipigs and at 4-10 min in one microminipig. The peak CEI and SIR values were 235.6 HU and 4.8 for venous angle, 239.4 HU and 2.1 for upper TD, and 387.3 HU and 2.1 for middle TD. The visibility and continuity of upper-middle TD scores were 4.0 and 3.3-3.7 for DCCTL, and 4.0 and 4.0 for DCMRL. In the injured lymphatic model, both DCCTL and DCMRL demonstrated lymphatic leakage. CONCLUSIONS: DCCTL and DCMRL in a microminipig model enabled excellent visualization of central lymphatic ducts and lymphatic leakage, indicating the research and clinical potential of both modalities. KEY POINTS: • Intranodal dynamic contrast-enhanced computed tomography lymphangiography showed a contrast enhancement peak at 5-10 min in all microminipigs. • Intranodal dynamic contrast-enhanced magnetic resonance lymphangiography showed a contrast enhancement peak at 2-4 min in two microminipigs and at 4-10 min in one microminipig. • Both intranodal dynamic contrast-enhanced computed tomography lymphangiography and dynamic contrast-enhanced magnetic resonance lymphangiography demonstrated the central lymphatic ducts and lymphatic leakage.

Early biomarkers for kidney injury in heat-related illness patients: a prospective observational study at Japanese Self-Defense Force Fuji Hospital.

BACKGROUND: Since heatstroke-induced acute kidney injury (AKI) can progress to chronic kidney disease, it would be useful to detect heatstroke-induced AKI and severe heat-related illness in the early phase. We studied the epidemiology of heat-related illness among patients in the Japanese Ground Self-Defense Force and evaluated the relationship between heat-related illness severity and early urinary biomarkers for AKI. METHODS: We enrolled patients who were diagnosed with heat-related illness at the Self-Defense Force Fuji Hospital from 1 May to 30 September 2020. We compared the urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), liver fatty acid-binding protein (L-FABP), N-acetyl-ß-D-glucosaminidase (NAG) and ß2-microglobulin levels according to the severity of heat-related illness as defined by positive scores for the Japanese Association of Acute Medicine Heatstroke Working Group (JAAM-HS-WG) criteria (0, mild; 1, moderate; ≥2, severe). RESULTS: Of the 44 patients, kidney injury, defined as serum creatinine (sCr) ≥1.2 mg/dL, was seen in 9 (20.5%) patients. Urinary NAG, NGAL and L-FABP levels were significantly higher in the ≥2 JAAM-HS-WG criteria group than in the 0 group. Furthermore, urinary L-FABP levels were positively correlated with sCr levels. In contrast, the urinary KIM-1 levels showed the best correlation with serum cystatin C (sCysC) among these biomarkers. CONCLUSIONS: We conclude even mild to moderate heatstroke could lead to AKI. Urinary L-FABP is useful for detecting heatstroke-induced AKI and patients with severe heat-related illness requiring immediate treatment. Urinary KIM-1 may detect heatstroke-induced AKI in terms of sCysC, although it was not related to the severity of heat-related illness.

Radiological Arterial Anatomy in Mature Microminipigs as a Pre-clinical Research Model in Interventional Radiology.

PURPOSE: To define the radiological arterial anatomy in mature microminipigs as a pre-clinical research animal model in interventional radiology. MATERIALS AND METHODS: Five female microminipigs (weighing 20.9 ± 2.9 kg) were used in this study. Under general anesthesia, computed tomography (CT) angiography was performed using a 16-slice CT scanner. CT was performed 12 s after initiation of an intravenous injection of 40 ml of nonionic contrast media at 3.0 ml/second using a power injector. The transverse CT angiography images were evaluated using a digital imaging and communication in medicine viewer, and the diameters of the following 41 arteries were measured.: ascending aorta, descending aorta, thoracoabdominal aorta, abdominal aorta, pulmonary artery trunk, both pulmonary, brachiocephalic artery, short common bicarotid, both common carotid artery, subclavian, bronchial, internal mammary, celiac, common hepatic, left lateral hepatic, middle hepatic, left hepatic, gastroduodenal, cranial duodenopancreatic, splenic, left gastric, cranial mesenteric, ileocolic , bilateral colic artery, caudal mesenteric, cranial rectal, renal, both external iliac arteries, internal iliac common trunk, and both internal iliac and femoral arteries. RESULTS: The microminipigs' vascular anatomy was the same as domestic pig anatomy and similar to human anatomy. The diameter of the aorta (ascending to abdominal) was 17.1-7.0 mm, iliac and femoral arteries (internal iliac common trunk to femoral artery): 5.5-3.8 mm, pulmonary arteries: 9.3-14.7 mm, and major first aortic branches (e.g., celiac or brachiocephalic artery): 2.2-9.2 mm. CONCLUSION: This study defined the microminipig arterial anatomy in the trunk.

Spatiotemporal imaging of redox status using in vivo dynamic nuclear polarization magnetic resonance imaging system for early monitoring of response to radiation treatment of tumor.

In general, the effectiveness of radiation treatment is evaluated through the observation of morphological changes with computed tomography (CT) or magnetic resonance imaging (MRI) images after treatment. However, the evaluation of the treatment effects can be very time consuming, and thus can delay the verification of patient cases where treatment has not been fully effective. It is known that the treatment efficacy depends on redox modulation in tumor tissues, which is an indirect effect of oxidizing redox molecules such as hydroxyl radicals and of reactive oxygen species generated by radiation treatment. In vivo dynamic nuclear polarization-MRI (DNP-MRI) using carbamoyl-PROXYL (CmP) as a redox sensitive DNP probe enables the accurate monitoring of the anatomical distribution of free radicals based on interactions of electrons and nuclear spin, known as Overhauser effect. However, spatiotemporal response of the redox status in tumor tissues post-irradiation remains unknown. In this study, we demonstrate the usefulness of spatiotemporal redox status as an early imaging biomarker of tumor response after irradiation using in vivo DNP-MRI. Our results highlight that in vivo DNP-MRI/CmP allowed us to visualize the tumor redox status responses significantly faster and earlier compared to the verification of morphological changes observed with 1.5 T MRI and cancer metabolism (Warburg effect) obtained by hyperpolarized 13C pyruvate MRS. Our findings suggest that the early assessment of redox status alterations with in vivo DNP-MRI/CmP probe may provide very efficient information regarding the effectiveness of the subsequent radiation treatment.

Imaging of Hydroxyl-Radical Generation Using Dynamic Nuclear Polarization-Magnetic Resonance Imaging and a Spin-Trapping Agent.

Reactive oxygen species (ROS) play an important role in cell metabolism, but they can cause oxidative damage to biomolecules. Among ROS, the hydroxyl radical (·OH) is one of the most reactive molecules in biological systems because of its high reaction rate constant. Therefore, imaging of ·OH could be useful for evaluation of the redox mechanism and diagnosis of oxidative diseases. In vivo dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) is a noninvasive imaging method to obtain spatiotemporal information about free radicals with MRI anatomical resolution. In this study, we investigated the visualization of hydroxyl radicals generated from the Fenton reaction by combining DNP-MRI with a spin-trapping agent (DMPO: 5,5-dimethyl-1-pyrroline N-oxide) for ·OH. Additionally, we demonstrated the radical-scavenging effect using four thiol-related reagents by DNP-MRI. We demonstrated that DNP enhancement could be induced by the DMPO-OH radical using the DNP-MRI/spin-trapping method and visualized ·OH generation for the first time. Maximum DNP enhancement was observed at an electron paramagnetic resonance irradiation frequency of 474.5 MHz. Furthermore, the radical-scavenging effect was simultaneously evaluated by the decrease in the DNP image value of DMPO-OH. An advantage of our methods is that they simultaneously investigate compound activity and the radical-scavenging effect.

Dynamic contrast-enhanced computed tomography lymphangiography with intranodal injection of water-soluble iodine contrast media in microminipig: imaging protocol and feasibility.

OBJECTIVES: To evaluate the optimal imaging protocol and the feasibility of intranodal dynamic contrast-enhanced computed tomography lymphangiography (DCCTL) in microminipigs. METHODS: The Committee for Animal Research and Welfare provided university approval. Five female microminipigs underwent DCCTL after inguinal lymph node injection of 0.1 mL/kg of iodine contrast media at a rate of 0.3 mL/min with three different iodine concentrations: group 1, 75 mgI/mL; group 2, 150 mgI/mL; and group 3, 300 mgI/mL. The CT values of the venous angle, thoracic duct (TD), cisterna chyli, iliac lymphatic duct, and iliac lymph node were measured; increases in CT values pre- to post-contrast were assessed as the contrast-enhanced index (CEI). Multi-detector row CT (MDCT) and volume rendering images showing the highest CEI were qualitatively evaluated. RESULTS: The CEI of all lymphatics peaked at 5-10 min. The mean CEI of TD at 10 min of group 2 (193.0 HU) and group 3 (201.5 HU) were significantly higher than that of group 1 (70.7 HU) (p = 0.024). The continuity and overall diagnostic acceptability of all lymphatic system components were better in group 3 (3.6 and 3.0, respectively) than group 1 (2.6 and 1.6) and group 2 (3.0 and 2.6) (p = 0.249 and 0.204). CONCLUSIONS: The optimal imaging protocol for intranodal DCCTL could be dual-phase imaging at 5 and 10 min after the injection of 300 mgI/mL iodinated contrast media. DCCTL provided good images of lymphatics and is potentially feasible in clinical settings. KEY POINTS: • Dynamic contrast-enhanced computed tomography lymphangiography with intranodal injection of water-soluble iodine contrast media showed the highest enhancement of all lymphatics at scan delays of 5 and 10 min. • The optimal iodine concentration for intranodal dynamic contrast-enhanced computed tomography lymphangiography might be 300 mgI/mL. • Intranodal dynamic contrast-enhanced computed tomography lymphangiography provided good images of all the lymphatic system components and is potentially feasible in clinical settings.

Nuclear Accumulation of ß-Catenin in Cancer Stem Cell Radioresistance and Stemness in Human Colon Cancer.

BACKGROUND/AIM: The aim of this study was to examine whether the Wnt/ß-catenin signal activation is a cause of radioresistance in colon cancer by assessing the ß-catenin localization and its correlation with cancer stem cells (CSCs). MATERIALS AND METHODS: The nuclear levels of ß-catenin, the hallmark of Wnt activation, were analyzed in HCT116 and SW480 cells by immunohistochemistry, before and after irradiation. Further, we assessed CSC populations by staining for aldehyde dehydrogenase-1 (ALDH1) and CD44. RESULTS: ß-catenin was localized predominantly in the nucleus and plasma membrane in SW480 and HCT116 cells, respectively. Compared to HCT116 cells, SW480 cells displayed higher Wnt activation. At 24 h after irradiation, most of the DSBs in SW480 cells were repaired, but were still present in HCT116 cells. Additionally, compared to HCT116 cells, a significantly higher proportion of SW480 cells were ALDH1- and CD44-positive. CONCLUSION: Colon cancers with nuclear ß-catenin accumulation demonstrated greater radio-resistance with a higher number of CSCs.