Contrast-enhanced Ultrasound Sonography Research Articles

Current aspects of multimodal ultrasound liver diagnostics using contrast-enhanced ultrasonography (CEUS), fat evaluation, fibrosis assessment, and perfusion analysis - An update.

Current ultrasound multifrequency probes allow both improved detail resolution and depth of penetration when examining the liver. Also, new developments in vascular diagnostics, elastography with fibrosis assessment, evaluation of possible steatosis, and parametric and time intensity curve (TIC) analysis of dynamic microvascularization of the liver with contrast-enhanced ultrasound sonography (CEUS) complement ultrasound-guided diagnostics. State-of-the-art high-resolution technology includes a high frame rate (HiFR) mode for CEUS, fast shear wave measurements with the sound touch quantify (STQ) mode, artifact-free flow detection using HR flow and glazing flow in combination with a special flow-adapted imaging (Ultra Micro Angiography, UMA) and additionally different assessments of possible fatty liver (UltraSound ATtenuation Imaging Technology, USAT). In 50 cases with focal liver lesions, a multimodal liver diagnosis was performed with a still new high-performance ultrasound system as part of the clarification of questions from the university liver consultation and tumor outpatient clinic.

Insulitis in Human Type 1 Diabetic Pancreas: From Stem Cell Grafting to Islet Organoids for a Successful Cell-Based Therapy

Type 1 diabetes (T1D) is an autoimmune disease with immune cells' islet infiltration (called "insulitis"), which leads to beta cell loss. Despite being the critical element of T1D occurrence and pathogenesis, insulitis is often present in a limited percentage of islets, also at diagnosis. Therefore, it is needed to define reproducible methods to detect insulitis and beta-cell decline, to allow accurate and early diagnosis and to monitor therapy. However, this goal is still far due to the morphological aspect of islet microvasculature, which is rather dense and rich, and is considerably rearranged during insulitis. More studies on microvasculature are required to understand if contrast-enhanced ultrasound sonography measurements of pancreatic blood-flow dynamics may provide a clinically deployable predictive marker to predict disease progression and therapeutic reversal in pre-symptomatic T1D patients. Therefore, it is needed to clarify the relation between insulitis and the dynamics of β cell loss and with coexisting mechanisms of dysfunction, according to clinical stage, as well as the micro vessels' dynamics and microvasculature reorganization. Moreover, the ideal cell-based therapy of T1D should start from an early diagnosis allowing a sufficient isolation of specific Procr+ progenitors, followed by the generation and expansion of islet organoids, which could be transplanted coupled to an immune-regulatory therapy which will permit the maintenance of pancreatic islets and an effective and long-lasting insulitis reversal.

Use of Contrast-Enhanced Ultrasound Sonography in Giant Cell Arteritis: A Proof-of-Concept Study.

C-Reactive protein and erythrocyte sedimentation rate are crucial parameters used to monitor giant cell arteritis (GCA). Given that tocilizumab is approved for the treatment of GCA, these parameters are less sensitive because of the effects of interleukin-6 receptor blockade. Thus, the optimal method for monitoring GCA patients undergoing tocilizumab therapy, especially patients exhibiting a persistent thickened vessel wall in large vessels, remains unclear. Contrast-enhanced ultrasonography (CEUS) can increase the visibility of tissue perfusion by slow blood flow, which cannot be detected by power color doppler. We used CEUS to investigate patients with active and inactive GCA of the large vessels (active large vessel arteritis [aLVV]/inactive large vessel arteritis [iLVV]) who were not administered tocilizumab in this proof-of-concept study. After injection of the ultrasound contrast agent, the contrasted area (CA) of large vessels in a transverse section was calculated twice: first when the lumen was contrasted completely and once again 4-8 s later. We investigated the value of increase in CA that exhibited the best sensitivity and specificity for aLVV. Twenty-four patients were included in this study: 15 with aLVV and 9 with iLVV. The CA increased from 32.2 ± 16.8 to 52.5 ± 21.3 mm2 (p < 0.0001) in aLVV. The mean CA remained unchanged in iLVV. The best cutoff value to differentiate between aLVV and iLVV was a ≥25% increase in CA with a sensitivity and specificity of 91.7% and 100%, respectively. Our study indicates that CEUS can detect aLVV with high sensitivity and specificity. Incorporation of CEUS into routine clinical practice might result in a good method for monitoring disease activity in LVV in GCA patients. The limitation of our study was the small number of patients and the lack of investigator blinding to clinical data.

Real-world Evidence of Diffusion-weighted Imaging Combined With Magnetic Resonance Cholangiopancreatography for Pancreatic Tumor Screening: A Cross-Sectional Diagnostic Accuracy Study.

The aim was to clarify the sensitivity and specificity of diffusion-weighted imaging, as well as of that in combination with magnetic resonance cholangiopancreatography for pancreatic tumor diagnosis in real-world clinical setting. Subjects were 217 consecutive patients who underwent both magnetic resonance imaging and contrast-enhanced ultrasound sonography. Cases positive for a pancreatic tumor were confirmed based on pathological diagnosis, whereas negative cases were defined when no solid pancreatic tumor was detected by contrast-enhanced ultrasound sonography or a solid mass was detected but the diagnosis was ultimately denied based on pathological results. Diffusion-weighted imaging-positive was defined as a case with high signals and magnetic resonance cholangiopancreatography-positive when localized main pancreatic duct stenosis with caudal dilation was detected.We calculated sensitivity and specificity of each modality and those in combination based on sequential use for pancreatic tumor diagnosis. Diffusion-weighted imaging showed a sensitivity of 94.4% and specificity of 94.5%, whereas those values for magnetic resonance cholangiopancreatography alone were 83.3% and 99.0%, respectively, and for the modalities in combination were 100% and 94.5%, respectively. Diffusion-weighted imaging was more sensitive than magnetic resonance cholangiopancreatography, whereas those used in combination resulted in increased sensitivity.

Contrast-enhanced ultrasound sonography combined with strain elastography to evaluate mandibular lymph nodes in clinically healthy dogs and those with head and neck tumors

Determining lymph node metastases in dogs with neoplasia is important in staging and developing a therapeutic plan. In this study, the clinical efficacy of combined lymphosonography and strain elastography was evaluated for its ability to identify metastatic mandibular lymph nodes. Data from clinically healthy dogs (n = 16) and those with head/neck tumors (n = 11) were enrolled. Strain elastographic patterns were classified according to the percentage of the stiffness lymph node area (grade 1–4/4). Lymphosonographic images were evaluated quantitatively (visualization of lymphatic vessels/lymph nodes; contrast transit time) and qualitatively (enhancement pattern). There was a significant difference in the strain elastographic pattern (P = 0.011) and lymphosonographic contrast enhancement (P = 0.001) in the metastatic nodes compared to clinical healthy or non-metastatic nodes. Mandibular lymph nodes with filling defects after lymphosonography and high-grade strain elastographic patterns suggested metastasis, and the combination of lymphosonography and strain elastography was useful for identifying malignancy.

Intra-Plaque Vessels on Contrast-Enhanced Ultrasound Sonography Predict Carotid Plaque Histology

Background and Purpose: Although the echogenicity of carotid plaques on carotid enhanced ultrasound (CEUS) was reported to correlate with the historological density of intra-plaque neovessels, it is unclear whether the intra-plaque vessel size is associated with carotid plaque vulnerability. We evaluated the relationship of size of intra-plaque vessels on CEUS with carotid plaque histology. Methods: We prospectively registered patients with carotid stenosis who were hospitalized to receive carotid endarterectomy between 2012 and 2016. CEUS was performed by ultrasound specialists using a 7-MHz linear transducer (GE LOGIQ7; GE Healthcare, Milwaukee, WN, USA). Sonazoid® was used for conducting CEUS. The sizes of microbubbles inside the plaques were scored at 0, 1, 3, and 5 min after the injection of contrast agent, and were categorized according to our defined vascular score (Vas-S; 0: the effect of contrast was not recognized; 1: the microbubbles were visible, but so blurred and vague that their shape could not be recognized; 2: dot or string-like microbubbles with movement, localized in part or the whole site of the plaque). At histological examination, we simplified the modified American Heart Association classification and defined as an atherosclerotic category (Ath-cat; 1: unruptured plaque; 2: ruptured plaque; 3: healed plaque). We then assessed the correlation of Vas-S with Ath-cat, which describes the process of rupture and restoration of carotid plaques. Results: A total of 97 patients were included in this study. A higher Ath-cat was significantly associated with higher Vas-S at any time. Spearman signed-rank test indicated that Vas-S at 1 min was most strongly correlated with Ath-cat (ρ = 0.43, p = 0.001). Receiver operating curve analysis indicated that a Vas-S of 0 at 1 min was significantly associated with an unruptured plaque (area under curve [AUC] 0.72, p = 0.006), while a Vas-S of 2 at 1 min was significantly associated with a healed plaque (AUC 0.72, p = 0.001). Conclusion: Vas-S values of 0 and 2 at 1 min indicated unruptured and healed plaques respectively. Thus, a Vas-S of 1 at 1 min is an indicator of a ruptured plaque. The intra-plaque vessel size on CEUS was significantly associated with carotid plaque histology, and may predict the process of plaque rupture and restoration.

Role of Contrast-Enhanced Ultrasound Sonography in the Medical Diagnostics of the Disease Activity in Patients With Takayasu Arteritis

The accurate diagnosis of Takayasu arteritis (TA) and the evaluation of its activity can bring significant challenges. In this paper, we sought to investigate a correlation between clinical activity and the enhancement of vessel wall acquired by contrast-enhanced ultrasound sonography (CEUS) in patients with TA, and to evaluate whether CEUS can be used to assess the disease activity of TA. Twenty TA patients with their carotid arteries affected were enrolled and divided into the active group and the inactive group according to the NIH scoring method. The white blood cell counts, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were obtained. Conventional ultrasound was performed to acquire the external diameter of the artery (D), intima-media thickness of the arterial wall (IMT), percent area stenosis, peak systolic velocity, end diastolic velocity, and resistance index. CEUS was performed to acquire the enhanced intensity (EI), derived peak intensity (DPI), and time to peak. The analysis showed that compared with the inactive group, D and IMT were significantly higher in the active group ( $6.50~\pm ~1.80$ versus $9.20~\pm ~4.00$ mm, $1.80~\pm ~0.40$ versus $2.40~\pm ~0.70$ mm, $p ). EI and DPI were also significantly higher in the active group ( $38.20~\pm ~10.62$ versus $80.80~\pm ~23.60$ IU, $46.20~\pm ~10.20$ versus $90.30~\pm ~24.60$ IU, $p ). Meanwhile, EI and DPI showed good correlation with CRP and ESR. Therefore, our study demonstrated that CEUS can increase the effectiveness of conventional ultrasound in differentiating active and inactive TA.

Ultrasonographic characteristics of hepatic neuroendocrine neoplasm

Objective To analyze the features of hepatic neuroendocrine neoplasm (HNEN) with conventional ultrasound and contrast-enhanced ultrasound sonography (CEUS), and to evaluate the value in the diagnosis and differential diagnosis of HNEN by ultrasound. Methods Fifty patients of HNEN confirmed pathologically or clinically were enrolled. All patients underwent conventional ultrasound and CEUS. Among the patients, 5 cases were primary hepatic neuroendocrine neoplasm (PHNEN), and 45 cases were metastatic hepatic neuroendocrine neoplasm (MHNEN). Conventional ultrasound and CEUS features of HNEN were analyzed and the distinctions between PHNEN and MHNEN were compared. Results Baseline ultrasound showed that 37 (74%) HNEN were multiple lesions located in liver, 23 (46%) lesions with hyperechoic appearance, 35 (70%) lesions with homogeneous echoic, 28 (56%) lesions were clearly marginated, 8 (16%) lesions were surrounded by acoustic halo, and 12 (24%) lesions with posterior echo attenuation. CEUS showed that the majority of HNEN exhibited the enhanced pattern of rapid wash-in and wash-out . Forty-six (92%) lesions showed hyper-enhancement in the arterial phase, 44 (88%) lesions showed iso-enhancement in the portal phase, and 47(94%) lesions showed hypo-enhancement in the late phase.Feeding vessels were observed in 31 (62%) lesions, intralesional non-enhancement zone was observed in 17(34%) lesions, and capsule enhancement in the delay phase was found in 10(20%) lesions. MHNEN had smaller diameter [ (3.92±2.77)cm vs (12.82±8.85)cm, P=0.004] and less likely to present cystic structure intralesional than PHNEN (1/45 vs 2/5, P 0.05). Conclusions HNEN has a certain characteristic that can be identified on ultrasonography. Ultrasound can provide some valuable information to diagnose HNEN. While it′s difficult to differentiate PHNEN and MHNEN owing to their similar ultrasonographic characteristics. Key words: Ultrasonography; Contrast-enhanced ultrasound; Liver neoplasms; Neuroendocrine neoplasms

Comparison of Contrast-Enhanced Ultrasound and Gadolinium-Ethoxybenzyl-Diethylenetriamine Pentaacetic Acid-Enhanced MRI for the Diagnosis of Macroscopic Type of Hepatocellular Carcinoma

Objective: We compared the efficacy of contrast-enhanced ultrasound sonography (CEUS) with sonazoid and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI for the assessment of macroscopic classification of nodular hepatocellular carcinoma (HCC). Methods: Seventy-seven consecutive patients with 79 surgically resected HCCs who underwent both preoperative CEUS and Gd-EOB-DTPA-enhanced MRI were enrolled in this retrospective study. Based on the macroscopic diagnosis of resected specimens, nodules were categorized into the simple nodular (SN) and non-SN type HCC. Two hepatologists independently assessed image datasets of the post-vascular phase of CEUS and hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI to compare their diagnostic performance. Results: Gd-EOB-DTPA-enhanced MRI enabled the evaluation of macroscopic classification in a significantly larger number of nodules than CEUS (78/79 (98.7%) vs. 70/79 (88.6%), p < 0.05). Of 70 nodules that could be evaluated by both modalities, 41 and 29 nodules were pathologically categorized as SN and non-SN, respectively. The areas under the receiver operating characteristic curve (AUC) for non-SN did not differ between CEUS and Gd-EOB-DTPA-enhanced MRI (reader 1: 0.748 for CEUS, 0.808 for MRI; reader 2: 0.759 for CEUS, 0.787 for MRI). The AUC of combined CEUS and Gd-EOB-DTPA-enhanced MRI for SN HCC was 0.855 (reader 1) and 0.824 (reader 2), indicating higher AUC values for the combined modalities. Conclusions: The diagnostic performance for macroscopic classification of nodular HCC of CEUS was comparable with that of Gd-EOB-DTPA-enhanced MRI, although some HCCs could not be evaluated by CEUS owing to lower detectability. The combination of the 2 modalities had a more accurate diagnostic performance.

Ultrasound and contrast enhanced ultrasound sonography evaluation of intestinal acute graft-vs-host disease

SUMMARY Intestinal acute graft-vs-host disease (I-GVHD) is a life-threatening complication after allografting. Non-invasive bedside procedures to evaluate extension and treatment response are still lacking. Standard ultrasound sonography (US) detects bowel wall thickening (BWT) in I-GVHD and helps to identify its extension (single or multiple sites at once). Color doppler US detects blood flow at arterioles level. Contrast-enhanced ultrasound sonography (CEUS) can detect microcirculation changes (MVC) of the bowel wall at capillary level, real time, and even bedside. CEUS allows evaluating, with dedicated software, quantitatively wash-in and washout curves of blood flowing through the thickened bowel wall, giving time intensity curves, which help to monitor treatment response as for Chron’s disease. Patients with I-GVHD with clinical relevant improvement may still have quiescent active disease. CEUS allows identifying, qualitatively and quantitatively, patients with I-GVHD with clinical improvement but with still active disease.

Prospective qualitative and quantitative non-invasive evaluation of intestinal acute GVHD by contrast-enhanced ultrasound sonography

Intestinal acute GVHD (I-aGVHD) is a life-threatening complication after allografting. Non-invasive bed-side procedures to evaluate extension and treatment response are still lacking. We hypothesized that, during I-aGVHD, contrast-enhanced ultrasound sonography (CEUS) could detect microcirculation changes (MVC) of the bowel wall (BW) and help to monitor treatment response. We prospectively employed CEUS in 83 consecutive patients. Of these, 14 patients with biopsy-proven intestinal GVHD (I-GVHD) were defined as the study group, whereas 16 patients with biopsy-proven stomach GVHD (U-GVHD) without intestinal symptoms, 6 normal volunteers and 4 patients with neutropenic enterocolitis were defined as the control group. All patients were evaluated with both standard ultrasonography (US) and CEUS at the onset of intestinal symptoms, during clinical follow-up and at flare of symptoms. Standard US revealed BW thickening of multiple intestinal segments, useful to determine the extension of GVHD. CEUS showed MVC, which correlated with GVHD activity, treatment response, and predicted flare of intestinal symptoms. US and CEUS findings were superimposable at diagnosis and in remission. CEUS was, however, more sensitive and specific to identify subclinical activity in patients with clinical relevant improvement. These findings were not observed in the control groups. CEUS is a non-invasive, easily reproducible bed-side tool useful to monitor I-aGVHD.