Improving artificial intelligence pipeline for liver malignancy diagnosis using ultrasound images and video frames.

Recent developments of deep learning methods have demonstrated their feasibility in liver malignancy diagnosis using ultrasound (US) images. However, most of these methods require manual selection and annotation of US images by radiologists, which limit their practical application. On the other hand, US videos provide more comprehensive morphological information about liver masses and their relationships with surrounding structures than US images, potentially leading to a more accurate diagnosis. Here, we developed a fully automated artificial intelligence (AI) pipeline to imitate the workflow of radiologists for detecting liver masses and diagnosing liver malignancy. In this pipeline, we designed an automated mass-guided strategy that used segmentation information to direct diagnostic models to focus on liver masses, thus increasing diagnostic accuracy. The diagnostic models based on US videos utilized bi-directional convolutional long short-term memory modules with an attention-boosted module to learn and fuse spatiotemporal information from consecutive video frames. Using a large-scale dataset of 50 063 US images and video frames from 11 468 patients, we developed and tested the AI pipeline and investigated its applications. A dataset of annotated US images is available at https://doi.org/10.5281/zenodo.7272660.

Contrast-enhanced ultrasound improves the potency of fine-needle aspiration in thyroid nodules with high inadequate risk.

BACKGROUND: This study aims to determine the clinical value of contrast enhanced ultrasound (CEUS) for fine-needle aspiration (FNA) of high inadequate risky thyroid nodules. METHODS: During April 2018 and April 2021, consecutive 3748 thyroid nodules underwent FNA were retrospectively analyzed. CEUS guided FNA (CEUS-FNA) was applied in 115 nodules with high inadequate risk in Lingnan Campus. Ten nodules underwent CEUS-FNA presented non-enhancing, and would be further analyzed independently. Other 105 partial or total enhancing nodules were included as CEUS-FNA group, and 210 nodules with high inadequate risk in Tianhe Campus were match as the US-FNA control group. FNA specimens were collected for liquid-based preparation. Cytological results were classified following the Bethesda System for Reporting Thyroid Cytopathology. RESULTS: The overall FNA specimen inadequate rate in our center was 6.6%. All of the ten non-enhancing nodules under CEUS have an inadequate result in cytopathological analyzes. The subsequent postoperative pathology and follow-up ultrasonography showed the non-enhancing nodules were benign or stable without further malignant features. Total specimen inadequate rate of high inadequate risk thyroid nodules in CEUS-FNA group was significantly lower than US-FNA group (6.7% vs. 16.7%, P = 0.014). Further stratified analyzed shown that FNA under US guidance, the inadequate rates in cystic, predominantly cystic, predominantly solid and solid sub-groups were 28.1%, 17.1%, 10.0% and 9.2% (P = 0.019). In contrast, the inadequate rates in cystic, predominantly cystic, predominantly solid and solid sub-groups were 7.4%, 6.7%, 5.6% and 6.7% (P = 0.996) in CEUS-FNA group. CONCLUSIONS: CEUS can improve the specimen adequacy of FNA in high inadequate risk thyroid nodules by avoiding unnecessary FNAs of the non-enhancing nodules, and accurately locating the viable tissue and precise guidance in real-time. CEUS is a recommend modality for FNA guidance of high inadequate risk thyroid nodules.

Acute transient swelling of the thyroid following fine-needle aspiration: A case series.

Acute transient swelling (ATS) of the thyroid is a rare complication following fine-needle aspiration (FNA) of thyroid nodules. We present 31 cases with 35 nodules encountered at our institute and reported in the literature, to provide further information. The incidence rate in our institute was 0.46%. Of these nodules, 74.3% (26/35) were solid, 65.7% (23/35) exhibited hypervascularity, and 77.2% (27/35) were benign or follicular neoplasms. Although most cases (87.1%, 27/31) occurred within 2 h after FNA, four patients experienced delayed ATS after 7 h to 2 days. Therefore, awareness of this complication, especially its delayed occurrence, should be raised.

Thyroid dysfunction following radiofrequency ablation for benign thyroid nodules: more likely to occur within one-week and in high-risk population.

BACKGROUND: Radiofrequency ablation (RFA) has been recommended as the treatment for benign thyroid nodules (BTNs) by some guidelines. However, detailed follow-up instructions for thyroid function about the timing and affected populations after RFA are lacked due to insufficient researches. This 12-month prospective study aimed to evaluate the incidence and risk factors of thyroid dysfunction at different time points after RFA, especially within 1 week that previous studies didn't concern. METHODS: Seventy-five euthyroid patients who underwent RFA for symptomatic BTNs were enrolled (ChiCTR-INR-16007884). The incidence of thyroid dysfunction within 1 week, at 1, 6, and 12 months after RFA was evaluated. The risk factors for different types of thyroid dysfunction in the different terms were further analyzed. RESULTS: Within 1 week after RFA, the incidence of thyroid dysfunction was as high as 36.00% unexpectedly, and only overt thyrotoxicosis and subclinical thyrotoxicosis occurred, which were significantly associated with the low-normal baseline thyrotropin (TSH) level (p = 0.001) and high ablation volume ratio (p = 0.008). From 1 to 12 months (the long term), the incidence dropped significantly and remained low (8.00-12.00%); and thyroid dysfunction presented as overt thyrotoxicosis, subclinical thyrotoxicosis, and subclinical hypothyroidism. The long-term thyrotoxicosis group had more cases with diabetes and lower baseline TSH levels. The long-term subclinical hypothyroidism group had more cases with positive thyroid peroxidase antibodies, higher baseline TSH levels, and higher ablation volume ratios. CONCLUSIONS: After the RFA of BTNs, thyroid dysfunction was more likely to occur within 1 week and in populations with risk factors.

Contrast-Enhanced Ultrasound for Biliary Ischemia: A Possible New Clinical Indication.

OBJECTIVES: Biliary perfusion is considered to contribute to biliary diseases, but routine imaging methods are insufficient to show it. This research investigated the ability of contrast-enhanced ultrasound (CEUS) for biliary perfusion in a biliary ischemia model. METHODS: This research consisted of 2 parts. First, to determine whether CEUS enhancement of the tiny biliary wall represents biliary perfusion, a vascular tracer was used as a reference to evaluate the consistency with the enhancement of the biliary wall on CEUS and the staining by the vascular tracer under the conditions of occluded and recovered biliary perfusion. In the second part, the ability of CEUS for biliary ischemia was further evaluated with microvascular density measurement as a reference. The enhancement patterns were assigned CEUS scores, in which higher scores meant more decreased enhancement, and the diagnostic ability of CEUS was assessed by a receiver operating characteristic curve analysis. RESULTS: The biliary wall was unstained by the vascular tracer and nonenhanced on CEUS when biliary perfusion was interrupted and was stained blue and enhanced after recovery. The biliary wall in the ischemia surgery group showed lower microvascular density measurements (P < .001), decreased enhancement levels (P < .001), and higher CEUS scores (P < .001). When a CEUS score of 3 or higher (obvious decrease of the biliary wall to hypoenhancement or nonenhancement in the arterial phase or rapid wash-out to nonenhancement in the portal venous phase) was applied, CEUS had sensitivity of 87.8%, specificity of 98.3%, accuracy of 93.8%, and an area under the receiver operating characteristic curve of 0.98. CONCLUSIONS: Contrast enhancement of the biliary wall on CEUS represents biliary perfusion and has reasonably good diagnostic performance for biliary ischemia in an experimental animal setting.

CXCR5-Overexpressing Mesenchymal Stromal Cells Exhibit Enhanced Homing and Can Decrease Contact Hypersensitivity.

Mesenchymal stromal cells (MSCs) can modulate inflammation and contribute to tissue regeneration and, thus, have emerged as a promising option for cell-based therapy. However, the ability of MSCs to migrate to injured tissues still needs to be improved. In this study, we investigated whether genetically engineered MSCs could exhibit increased migratory properties and improved therapeutic efficacy. Using a mouse model of contact hypersensitivity (CHS), chemokine gene expression screening revealed that CXCL13 changed most significantly in injured tissue. Unfortunately, MSCs hardly express the corresponding receptor, CXCR5. Thus, CXCR5-overexpressing MSCs (MSCCXCR5) were generated that retained their abilities of proliferation, differentiation, and immunomodulation. Furthermore, MSCCXCR5 showed significantly increased migrating ability toward CXCL13. Importantly, systemic infusion of MSCCXCR5 dramatically suppressed CHS in mice, as evidenced by decreased levels of inflammatory cell infiltration and pro-inflammatory cytokine production. Numerous MSCCXCR5 migrated into inflamed ears, localized with T cells, inhibited T cell proliferation, promoted T cell apoptosis, and suppressed the production of T cell-derived pro-inflammatory factors. Collectively, these findings demonstrate that CXCR5 overexpression increases the ability of MSCs to respond to migratory stimuli and highly intensifies their immunomodulatory effects in vivo. This strategy for enhancing targeted stem/progenitor cell homing may improve the efficacy of MSC-based therapies.

In vitro heat insulation efficacy of 5% dextrose versus 0.9% saline during radiofrequency ablation.

PURPOSE: This study compared the efficacy of heat insulation between 5% dextrose and 0.9% saline in radiofrequency ablation (RFA). Accordingly, temperature variations and maximum temperatures were assessed at identical distances and heat field distributions. METHODS: Cubes of porcine liver tissue, measuring 10 mm across, were selected to precisely align the ablation boundary with the tissue boundary. An 18-gauge electrode with a 7-mm tip was inserted into each cube (10 per group) in a stainless-steel cup containing 40 mL of 5% dextrose or 0.9% saline. Fixed ablation was performed for 3 minutes using continuous mode at 30 W, simulating the typical thermal environment during thyroid RFA. Real-time temperature measurements were recorded by sensors positioned 0, 1, 3, and 5 mm from the cube's edge. A comparative analysis was conducted to assess the maximum temperature, temperature variation, and duration of temperatures exceeding 42℃. RESULTS: In both groups, the temperature curve declined with increasing distance from the edge of the ablated tissue. However, 0.9% saline exhibited higher maximum temperatures at 1, 3, and 5 mm compared to 5% dextrose (1 mm: 44.55°C±5.25°C vs. 34.68°C±3.07°C; 3 mm: 39.64°C±2.53°C vs. 29.22°C±2.21°C; 5 mm: 38.86°C±2.14°C vs. 28.74°C±2.51°C; all P<0.001). Considering a nerve injury threshold of 42°C, the 0.9% saline also displayed a greater proportion of samples reaching this temperature and a longer duration of temperatures exceeding it (P<0.05). CONCLUSION: The heat insulation efficacy of 5% dextrose at 1-5 mm exceeds that of 0.9% saline at identical distances and in a common thermal environment during thyroid RFA.

The two-year prognosis of multinodular goiter following radiofrequency ablation: based on all nodule burdens.

OBJECTIVE: Few studies used all nodule burdens to specify the prognosis of multinodular goiter (MNG) following radiofrequency ablation (RFA), so this study addresses this question for MNG after completely ablating dominant nodules. METHODS: The RFA indications for MNG included a total of 2-5 benign nodules with over 50% normal tissue on ultrasound, 1-3 well-defined benign dominant nodules on cytology, largest diameter ≥20 mm and/or with clinical complaints, and patient refusal or unable of surgery. A retrospective study of 185 MNG patients with completely ablated dominant nodules in a single-session RFA was conducted. The efficacy and complications were evaluated at 1, 6, 12 months and yearly thereafter. Based on retreatment risks, progressive disease (PD), stable disease (SD) and complete relief (CR) were introduced to assess all nodule load changes. PD was clarified as having new/non-target nodules newly appeared to ACR TI-RADS≥4, or new/enlarged non-target nodules ≥1 cm. RESULTS: The initial ablation ratios of target nodules were 100% at one month. During a mean 22.38±13.75 months (range, 12-60 months), the VRR of ablated nodules was 98.25% at 24 months without regrowth. Cosmetic and symptomatic scores decreased to 1 and 0, respectively, after 48 months. 9.7% of patients (18/185) had PD and the retreatment rate was 2.2% (4/185). The complication rate was 2.7% (5/185). CONCLUSIONS: RFA provides cosmetic and symptomatic relief for an average of two years. RFA is an useful minimally invasive treatment modality for selected MNG patients.

A novel parallel overlapping mode for complete ablation of large benign thyroid nodules in a single-session radiofrequency ablation.

Background: Radiofrequency ablation (RFA) has been widely applied in patients with benign thyroid nodules (BTNs), and complete ablation in a single-session treatment brings great benefits to patients. While how the ablation should be planned and performed to achieve complete ablation in a single-session treatment in large BTNs remains unknown. Purpose: To determine a more suitable ablation strategy for sufficient treatment in a single-session treatment. Materials and Methods: This retrospective study included 108 BTNs receiving RFA treatment. These patients were divided into two groups: group A using one insertion point with a fan-shaped overlapping mode and group B using multiple insertion points with a novel parallel overlapping mode. All the treatments used a hydrodissection approach and moving-shot technique. Contrast-enhanced ultrasonography (CEUS) was used to guide the supplementary ablation. Follow-ups were performed at 1, 3, 6 and 12 months. The rates of supplementary ablation, initial ablation ratio (IAR), the rates of complete ablation (CAR), treatment effects and complications between the two groups were compared. Results: The group B had larger treated nodules (10.2ml vs 6.4ml, P<0.001) than group A, while group B had a lower rate of supplementary ablation (21.6% vs 75.4%, P<0.001), especially in the BTNs with craniocaudal diameters ≥30mm (22.0% vs 100%, P<0.001). With the assistance of supplementary ablation, both groups achieved similar IAR (100% vs 100%, P=0.372) and CAR (94.7% vs 94.1%, P=1.000). Two groups showed similar VRRs at 12-month follow-up (77.9% vs 77.5%, P=0.894) and similar rates of complications (3.5% vs 2.0%, P=1.000). Conclusions: Needle placement using the multiple insertion points with a novel parallel overlapping mode would be easier to achieve complete ablation with less supplementary ablation, especially in large nodules.

Continuous, Large-Volume Hydrodissection to Protect Delicate Structures around the Thyroid throughout the Radiofrequency Ablation Procedure.

INTRODUCTION: Small-volume hydrodissection liquid dissipates rapidly and confers only short-term protection during radiofrequency ablation (RFA) of benign thyroid nodules. The aim of this study was to establish a safe method for continuous, large-volume hydrodissection. METHODS: A long needle was inserted and positioned outside the thyroid capsule; 5% glucose was injected to maintain a 3- to 5-mm continuous safety buffer. From October 2015 to July 2020, 166 patients underwent hydrodissection with different volumes, and ablation efficacy and complications associated with different liquid volumes (≤40 mL vs. >40 mL) were compared at 1-month postprocedure. Moreover, 20 mL liquid (equivalent to 250 mL in the human body) was injected around the thyroid of a rhesus monkey, after which CT scans were used to visualize the liquid's fate and verify its safety. RESULTS: The 51 patients with 10-40 mL injections and 116 patients with larger injections (45-450 mL) showed similar complete ablation rates (88.46% vs. 90.44%, p = 0.582), comparable 6-month VRR (82.79% vs. 76.62%, p = 0.079), and complication incidences, although the latter group had larger nodules (9.11 mL vs. 13.79 mL, p = 0.003), more energy delivered (3.44 kcal vs. 6.04 kcal, p < 0.001), and longer operation times (51.37 min vs. 69.2 min, p < 0.001). In the animal experiment, the 20 mL of liquid diffused quickly (within 10 min) from the vicinity of the thyroid to the mediastinum and retropharyngeal space. It was observed in the kidneys at 10 min and disappeared from the neck and chest space by 24 h. CONCLUSIONS: Continuous, large-volume hydrodissection can protect the delicate structures around the thyroid throughout the RFA procedure and might be beneficial in large thyroid nodule ablation.

mRNA-engineered mesenchymal stromal cells expressing CXCR2 enhances cell migration and improves recovery in IBD.

Mesenchymal stromal cells (MSCs) have shown significant heterogeneity in terms of therapeutic efficacy for inflammatory bowel disease (IBD) treatment, which may be due to an insufficient number of MSCs homing to the damaged tissue of the colon. Engineering MSCs with specific chemokine receptors can enhance the homing ability by lentiviral transduction. However, the unclear specific chemokine profile related to IBD and the safety concerns of viral-based gene delivery limit its application. Thus, a new strategy to modify MSCs to express specific chemokine receptors using mRNA engineering is developed to evaluate the homing ability of MSCs and its therapeutic effects for IBD. We found that CXCL2 and CXCL5 were highly expressed in the inflammatory colon, while MSCs minimally expressed the corresponding receptor CXCR2. Transient expression of CXCR2 in MSC was constructed and exhibited significantly enhanced migration to the inflamed colons, leading to a robust anti-inflammatory effect and high efficacy. Furthermore, the high expression of semaphorins7A on MSCs were found to induce the macrophages to produce IL-10, which may play a critical therapeutic role. This study demonstrated that the specific chemokine receptor CXCR2 mRNA-engineered MSCs not only improves the therapeutic efficacy of IBD but also provides an efficient and safe MSC modification strategy.

Contrast-enhanced ultrasonography to evaluate risk factors for short-term and long-term outcomes after liver transplantation: A pilot prospective study.

PURPOSE: To evaluate whether Doppler ultrasonography (DUS) and contrast-enhanced ultrasonography (CEUS) can identify liver donation after brain death (DBD) and cardiac death (DCD) with the risk of developing short-term primary graft dysfunction (PGD) or arterial and biliary complications within 1 year. MATERIALS AND METHODS: Consecutive DBD and DCD donors who underwent DUS/CEUS examinations before surgical procurement from February 2016 to June 2018 at our institution were included. The US and CEUS images of each donor liver were analysed, and the parameters were recorded. RESULTS: The mean time for US examination was 32 min (range, 20-59 min), and all donors tolerated the examination well. In terms of short-term outcomes, among the 52 eligible donor livers, 20 (38.5 %) of their recipients developed PGD. The multivariable analysis showed that decreased enhancement of donor livers on CEUS (OR = 15.976, 95 % CI: 1.652-154.628, P = 0.017) and high recipient model for end-stage liver disease (MELD) scores (OR = 1.050, 95 % CI: 1.004-1.099, P = 0.034) before liver transplantation (LT) were independent factors of PGD. In contrast, for long-term complications, among the 48 eligible donor livers, 16 (33.3 %) developed arterial or biliary complications within 1 year. The multivariable analysis did not show any independent factors of arterial or biliary complications within 1 year. CONCLUSIONS: A decrease in enhancement on CEUS is an independent risk factor for poor short-term outcomes of LT. CEUS may be promising for predicting post-LT outcomes of critically ill donors effectively and safely by evaluating the haemodynamic changes in DBD and DCD donor livers.

Doppler ultrasonography and contrast-enhanced ultrasonography to evaluate liver allograft discard: A pilot prospective study.

BACKGROUND: Broad hemodynamic changes, is believed to have a profoundly damaging effect on donor livers after brain death (DBD) or cardiac death (DCD). It remains unclear whether Doppler ultrasonography (DUS) and contrast-enhanced ultrasonography (CEUS), the imaging modalities to evaluate perfusion, could provide more information of liver discarded. OBJECTIVE: To evaluate the ability of DUS and CEUS to predict the risk of DBD or DCD liver discarded. METHODS: The consecutive DBD or DCD donors with DUS/CEUS examinations before surgical procurement from February 2016 to June 2018 at our institution were included. The US and CEUS images of each donor liver were analyzed and the parameters were recorded. RESULTS: Among the 67 eligible donor livers, 15 (22.4%) were discarded and 52 (77.6%) were used. The discarded livers showed prolonged SAT of hepatic artery (0.08s vs 0.06s, OR = 2.169, P = 0.008) on DUS, less cases with homogeneous enhancement (40.0% vs 73.1%, OR = 0.243, P = 0.028) on CEUS, more cases with decreased enhancement (53.3% vs 19.2%, OR = 4.800, P = 0.009), and less difference of the peak time between portal vein and liver parenchymal (0.5s vs 6.7s, OR = 0.917, P = 0.034). The multivariable analysis showed that donor liver with prolonged SAT of hepatic artery (OR = 7.304, 95% CI: 1.195-44.655, P = 0.031) and decreased enhancement (OR = 2.588, 95% CI: 1.234-5.426, P = 0.012) were independent factors of liver discarded. CONCLUSIONS: DUS/CEUS could be applied as a promising predictive tool to screen high-risk liver donors. The prolonged SAT of hepatic artery on DUS and the decrease of liver donor in enhancement on CEUS, indicating hemodynamic changes in DBD and DCD donor livers, were risk factors of liver discarded.

A Novel Strategy for Single-Session Ultrasound-Guided Radiofrequency Ablation of Large Benign Thyroid Nodules: A Pilot Cohort Study.

Background: Ultrasound-guided radiofrequency ablation (RFA) of thyroid nodules (TNs) is a minimally invasive procedure that has been widely used to induce volume reduction in symptomatic solid benign TNs. The goal of this study was to investigate a novel therapeutic approach for single-session ablation of large thyroid nodules (LTNs, vol > 20 ml). Methods: We performed a pilot cohort study of 21 patients with symptomatic solid benign LTNs (vol > 20 ml), who accepted ultrasound-guided RFA treatment between September 2018 and November 2019. RFA was performed using an 18-gauge internally cooled electrode with ultrasonographic guidance in a single session combined with intraoperative hydrodissection and immediate contrast-enhanced ultrasound (CEUS) to optimize safety and efficacy. Nodule volume was evaluated before ablation and at 1, 3, and 6 months after initial ablation, and all patients were asked to assess the cosmetic score (from 1 to 4) and symptom score (from 0 to 10) before ablation and at every follow-up after ablation. Results: At the 6 month follow-up, there was significant nodule volume reduction, from 27.49 ml ± 7.9 (standard deviation) to 3.82 ml ± 5.02 (p = 0.001). Cosmetic signs (p = 0.001) and pressure symptoms (p = 0.001) were significantly improved. All patients underwent RFA without any major complications, and very few patients developed a change in voice (2/21). However, the changes subsided within 1 month. Almost half of the patients received an additional RFA (11/21) treatment to achieve complete ablation on the intraoperative immediate CEUS evaluation. Conclusion: RFA is effective for treating LTNs (vol > 20 ml) and controlling clinical symptoms with a low complication rate. Patients were satisfied with cosmetic sign and pressure symptom improvement. The intraoperative hydrodissection and immediate CEUS represent a novel therapeutic approach for single-session ablation of LTNs.

Management of bleeding associated with radiofrequency ablation of benign thyroid nodules.

OBJECTIVE: This study was performed to explore the effective management of bleeding associated with radiofrequency ablation (RFA) of benign thyroid nodules. METHODS: Thirty-five patients with benign thyroid nodules who were treated with ultrasound-guided RFA from July 2015 to December 2016 at the Third Affiliated Hospital of Sun Yat-sen University were retrospectively reviewed. The technique efficacy, bleeding, and other complications were assessed during the follow-up period. RESULTS: The mean technique efficacy was 55.6%±22.8% at 1 month and 24.1%±17.1% at 6 months after the procedure. One case of an intranodular haematoma and two cases of voice change (>1 month) were observed. All patients recovered with corresponding treatment. CONCLUSION: Although the incidence of haemorrhage is low, serious haematomas are life-threatening. Therefore, having a comprehensive understanding of the potential complications, an accurate clinical strategy, and adequate technical skills may prevent or help to properly manage these complications.