Monitoring Progression of Ductal Carcinoma In Situ Using Photoacoustics and Contrast-Enhanced Ultrasound.

Breast cancer is the leading form of cancer in women, accounting for approximately 41,400 deaths in 2018. While a variety of risk factors have been identified, physical exercise has been linked to reducing both the risk and aggressiveness of breast cancer. Within breast cancer, ductal carcinoma in situ (DCIS) is a common finding. However, less than 25% of DCIS tumors actually progress into invasive breast cancer, resulting in overtreatment. This overtreatment is due to a lack of predictive precursors to assess aggressiveness and development of DCIS. We hypothesize that tissue oxygenation and perfusion measured by photoacoustic and contrast-enhanced ultrasound imaging, respectively, can predict DCIS aggressiveness. To test this, 20 FVB/NJ and 20 SV40Tag mice that genetically develop DCIS-like breast cancers were divided evenly into exercise and control groups and imaged over the course of 6 weeks. Tissue oxygenation was a predictive precursor to invasive breast cancer for FVB/NJ mice (P = 0.015) in the early stages of tumor development. Meanwhile, perfusion results were inconclusive (P \u3e 0.2) as a marker for disease progression. Moreover, voluntary physical exercise resulted in lower weekly tumor growth and significantly improved median survival (P = 0.014)

Scanning for QI: Outcomes from a Resident and Sonographer Driven Improvement of Radiology Resident Ultrasound Technique

Objective The aim of this structural quality improvement (QI) project was to improve the educational ultrasound curriculum. We created the pilot for an enduring addition to the radiology residency at Jefferson, with plans to include additional ultrasound examinations as the curriculum becomes more robust. Stakeholders included not only the radiology residency, which would benefit from improved resident education and knowledge, but also the hospital and ultimately patients, who stand to benefit from improved delivery of care

Ultrasound Quantitative Assessment of Ventral Finger Microvasculopathy in Systemic Sclerosis With Raynaud’s Phenomena: A Comparative Study

Objective: To assess the finger vascularity of systemic sclerosis patients with Raynaud\u27s phenomenon (RP-SSc) using various ultrasound techniques. Methods: All fingers (except thumbs) of 18 RP-SSc patients and 18 controls were imaged at room temperature using four ultrasound vascular imaging techniques. The percent vascular area was quantified by counting blood flow pixels in a 25 mm2 square centred at the nail fold for the dorsal side and in 25 mm2 and 100 mm2 square from the fingertip for the ventral side. The mean vascular intensity was calculated from the corresponding areas for dorsal and ventral sides. Results: The percent vascular areas and mean vascular intensities in RP-SSc were significantly lower than those in controls for both dorsal and ventral sides (p\u3c0.01). The mean vascular intensities showed slightly higher area under the curve (AUC) than the percent vascular areas (0.53-0.91 vs 0.53-0.90) regardless of imaging technique and assessment side. For each imaging technique, the ventral side vascularity showed a higher AUC (0.74-0.91) compared with the dorsal side (0.53-0.81). Moreover, ventral side abnormalities were associated with a history of digital ulcers. Conclusions: Ultrasound demonstrated potential to quantify finger vascularity of RP-SSc. The ventral side of the fingers showed a higher accuracy in detecting RP-SSc than the dorsal side

Contrast-Enhanced Ultrasound LI-RADS: A Pictorial Review

The American College of Radiology has implemented the Liver Imaging Reporting and Data System (LI-RADS) to help detect, interpret, and guide the management of suspected lesions on surveillance imaging for hepatocellular carcinoma (HCC) in patients with cirrhosis. The classification of indeterminate nodules with a grading algorithm can be used for multiple imaging modalities (US, CT, and MRI) and incorporates multiple imaging features to appropriately classify observations with different likelihood of being HCC. Contrast-enhanced ultrasound (CEUS) LI-RADS has been fully implemented since 2017. The aim of this pictorial article is to provide a comprehensive review of CEUS LI-RADS utilization, discuss its advantages, and highlight areas for potential improvement

Development of a Dual Drug-Loaded, Surfactant-Stabilized Contrast Agent Containing Oxygen

Co-delivery of cancer therapeutics improves efficacy and encourages synergy, but delivery faces challenges, including multidrug resistance and spatiotemporal distribution of therapeutics. To address these, we added paclitaxel to previously developed acoustically labile, oxygen-core, surfactant-stabilized microbubbles encapsulating lonidamine, with the aim of developing an agent containing both a therapeutic gas and two drugs acting in combination. Upon comparison of unloaded, single-loaded, and dual-loaded microbubbles, size (~1.7 µm) and yield (~2 × 109 microbubbles/mL) (~1.7) were not statistically different, nor were acoustic properties (maximum in vitro enhancements roughly 18 dB, in vitro enhancements roughly 18 dB). Both drugs encapsulated above required doses calculated for head and neck squamous cell carcinoma, the cancer of choice. Interestingly, paclitaxel encapsulation efficiency increased from 1.66% to 3.48% when lonidamine was included. During preparation, the combination of single drug-loaded micelles gave higher encapsulation (µg drug/g microbubbles) than micelles loaded with either drug alone (lonidamine, 104.85 ± 22.87 vs. 87.54 ± 16.41), paclitaxel (187.35 ± 8.38 vs. 136.51 ± 30.66). In vivo intravenous microbubbles produced prompt ultrasound enhancement within tumors lasting 3-5 min, indicating penetration into tumor vasculature. The ability to locally destroy the microbubble within the tumor vasculature was confirmed using a series of higher intensity ultrasound pulses. This ability to locally destroy microbubbles shows therapeutic promise that warrants further investigation

Contrast-enhanced Ultrasound Assessment of Treatment Response in a Patient with Multifocal Hepatocellular Carcinoma Treated with Transarterial Chemo and Radioembolization

Minimally invasive locoregional therapies have become important treatment options for patients with intermediate or late-stage hepatocellular carcinoma (HCC) who are ineligible for surgical resection or liver transplantation. Imaging modalities are essential for procedural guidance and for assessing treatment response thereafter. We report a unique finding of a patient with multifocal HCC treated with transarterial radioembolization (TARE) with yttrium-90 (Y90) and transarterial chemoembolization (TACE). We compared contrast-enhanced ultrasound (CEUS) with contrast-enhanced magnetic resonance imaging (CE-MRI) in the evaluation of treatment response to demonstrate advantages of CEUS imaging technique and its early detection of viable tumor

Longitudinal Ultrasound Imaging and Network Modeling in Rats Reveal Sex-Dependent Suppression of Liver Regeneration After Resection in Alcoholic Liver Disease

Liver resection is an important surgical technique in the treatment of cancers and transplantation. We used ultrasound imaging to study the dynamics of liver regeneration following two-thirds partial hepatectomy (PHx) in male and female rats fed via Lieber-deCarli liquid diet protocol of ethanol or isocaloric control or chow for 5–7 weeks. Ethanol-fed male rats did not recover liver volume to the pre-surgery levels over the course of 2 weeks after surgery. By contrast, ethanol-fed female rats as well as controls of both sexes showed normal volume recovery. Contrary to expectations, transient increases in both portal and hepatic artery blood flow rates were seen in most animals, with ethanol-fed males showing higher peak portal flow than any other experimental group. A computational model of liver regeneration was used to evaluate the contribution of physiological stimuli and estimate the animal-specific parameter intervals. The results implicate lower metabolic load, over a wide range of cell death sensitivity, in matching the model simulations to experimental data of ethanol-fed male rats. However, in the ethanol-fed female rats and controls of both sexes, metabolic load was higher and in combination with cell death sensitivity matched the observed volume recovery dynamics. We conclude that adaptation to chronic ethanol intake has a sex-dependent impact on liver volume recovery following liver resection, likely mediated by differences in the physiological stimuli or cell death responses that govern the regeneration process. Immunohistochemical analysis of pre- and post-resection liver tissue validated the results of computational modeling by associating lack of sensitivity to cell death with lower rates of cell death in ethanol-fed male rats. Our results illustrate the potential for non-invasive ultrasound imaging to assess liver volume recovery towards supporting development of clinically relevant computational models of liver regeneration

Contrast-Enhanced Ultrasound LI-RADS: A Pictorial Review

The American College of Radiology has implemented the Liver Imaging Reporting and Data System (LI-RADS) to help detect, interpret, and guide the management of suspected lesions on surveillance imaging for hepatocellular carcinoma (HCC) in patients with cirrhosis. The classification of indeterminate nodules with a grading algorithm can be used for multiple imaging modalities (US, CT, and MRI) and incorporates multiple imaging features to appropriately classify observations with different likelihood of being HCC. Contrast-enhanced ultrasound (CEUS) LI-RADS has been fully implemented since 2017. The aim of this pictorial article is to provide a comprehensive review of CEUS LI-RADS utilization, discuss its advantages, and highlight areas for potential improvement

Contrast-Enhanced Endoscopic Ultrasound for Identification of Sentinel Lymph Nodes in Esophageal Cancer

Introduction: In esophageal carcinoma, lymph node involvement is a crucial aspect of nodal staging and determining treatment strategies. Although grayscale endoscopic ultrasound (EUS) is the standard of care for staging, it is unable to identify lymph node drainage from primary tumors or sentinel lymph nodes (SLN). The goal of this study was to determine if Contrast Enhanced Endoscopic Ultrasound (CE- EUS) is superior to EUS in the identification of SLNs and nodal staging in esophageal carcinoma. Methods: In the unblinded pilot study, patients with newly diagnosed esophageal carcinoma were recruited to undergo CE-EUS and standard EUS. EUS was performed and visible lymph nodes were noted. The contrast agent, Sonazoid was injected peri-tumorally. Fine needle aspiration (FNA) was performed on all lymph nodes considered suspicious by either modality. Specimens were compared, using cytology as a reference. Results: 55 peri-esophageal lymph nodes were collected from 14 enrolled patients, with tumor staging of T2 and T3. 10 nodes identified as suspicious by EUS and 19 nodes identified as suspicious by CE-EUS were sampled by FNA. 4 nodes (40% cytologic yield) identified by EUS and 12 nodes (63% cytologic yield) identified by CE-EUS showed signs of metastatic disease. Nodal staging was upgraded in 4 patients (29%) with the addition of SLNs identified by CE-EUS. Discussion: CE-EUS may increase the identification of SLNs and increase cytologic yield that would not have normally been biopsied using EUS. This increase in SLN identification and cytologic yield can provide more accurate lymph node staging in esophageal carcinoma. Further study is indicated

Improved Tumor Control Following Radiosensitization with Ultrasound-Sensitive Oxygen Microbubbles and Tumor Mitochondrial Respiration Inhibitors in a Preclinical Model of Head and Neck Cancer

Tumor hypoxia (oxygen deficiency) is a major contributor to radiotherapy resistance. Ultrasound-sensitive microbubbles containing oxygen have been explored as a mechanism for overcoming tumor hypoxia locally prior to radiotherapy. Previously, our group demonstrated the ability to encapsulate and deliver a pharmacological inhibitor of tumor mitochondrial respiration (lonidamine (LND)), which resulted in ultrasound-sensitive microbubbles loaded with O2 and LND providing prolonged oxygenation relative to oxygenated microbubbles alone. This follow-up study aimed to evaluate the therapeutic response to radiation following the administration of oxygen microbubbles combined with tumor mitochondrial respiration inhibitors in a head and neck squamous cell carcinoma (HNSCC) tumor model. The influences of different radiation dose rates and treatment combinations were also explored. The results demonstrated that the co-delivery of O2 and LND successfully sensitized HNSCC tumors to radiation, and this was also enhanced with oral metformin, significantly slowing tumor growth relative to unsensitized controls (p \u3c 0.01). Microbubble sensitization was also shown to improve overall animal survival. Importantly, effects were found to be radiation dose-rate-dependent, reflecting the transient nature of tumor oxygenation