Browsing by Author "Javed, Kulsoom"
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Item Monitoring Acute Changes in Pancreatic Tumor Perfusion with Contrast-Enhanced Ultrasound and Photoacoustic Imaging Following Targeted Hyaluronic Acid Treatment(2020-05) Javed, Kulsoom; Hoyt, KennethPancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer related deaths. Early diagnosis is crucial for treating PDAC but is unlikely due to the asymptomatic nature of the tumor in early stages. PDAC is usually diagnosed in late stages when it cannot be resected and is not responsive to chemotherapy (chemoresistance). The chemoresistance and late symptoms are mostly due to the presence of hyaluronan (HA, glycosaminoglycan) in the extracellular matrix (ECM). HA is a marker of tumor aggression and is hydrophilic. It retains water molecules and forms a gel-fluid phase which increases the tumor interstitial pressure, collapses the tumor microvasculature, and causes chemoresistance. HA can be degraded by an enzyme, pegylated pancreatic hyaluronidase (PEGPH20; targeted HA treatment), into its subunits. The aim of this study was to monitor the acute changes in tumor perfusion with contrast enhanced ultrasound and photoacoustic imaging following HA removal by PEGPH20. Athymic nude mice (N=18) were implanted subcutaneously in the peri-tibial region of the right leg with 2 million pancreatic cancer cells. Contrast enhanced ultrasound (CEUS) and photoacoustic (PA) imaging studies were conducted at baseline (0 h) and at 6 h. A single dose of PEGPH20 (treatment) or saline (control) was injected at baseline. After the targeted removal of HA by PEGPH20, the tumor microvasculature expanded and an increase in tumor perfusion parameters; peak enhancement (PE) and wash-in rate (WiR) measured by CEUS, and total hemoglobin signal (HbT) and oxygen saturation (sO2) measured by PA was seen. These changes in CEUS and PA measures were confirmed by histological analysis of the excised tumor tissue. In conclusion, we saw a 50% increase in perfusion parameters at 6 h post treatment as compared to the control group. These acute changes in pancreatic tumor tissue can be monitored noninvasively by CEUS and PA imaging within 6 h of HA removal by PEGPH20.Item Monitoring Early Breast Cancer Response To Neoadjuvant Therapy Using H-Scan Ultrasound Imaging: Preliminary Preclinical Results(John Wiley and Sons Ltd., 2019-04-17) Khairalseed, Mawia; Javed, Kulsoom; Jashkaran, G.; Kim, J. -W; Parker, K. J.; Hoyt, Kenneth; Hoyt, Kenneth; Khairalseed, Mawia; Javed, KulsoomObjective—H-scan imaging is a new ultrasound technique used to visualize the relative size of acoustic scatterers. The purpose of this study was to evaluate the use of H-scan ultrasound imaging for monitoring early tumor response to neoadjuvant treatment using a preclinical breast cancer animal model. Methods—Real-time H-scan ultrasound imaging was implemented on a programmable ultrasound scanner (Vantage 256; Verasonics Inc., Kirkland, WA) equipped with an L11-4v transducer. Bioluminescence and H-scan ultrasound was used to image luciferase-positive breast cancer–bearing mice at baseline and at 24, 48, and 168 hours after administration of a single dose of neoadjuvant (paclitaxel) or sham treatment. Animals were euthanized at 48 or 168 hours, and tumors underwent histologic processing to identify cancer cell proliferation and apoptosis. Results—Baseline H-scan ultrasound images of control and therapy group tumors were comparable, but the latter exhibited significant changes over the 7-day study (P 0.40, P < .04). Conclusion—Preliminary preclinical results suggest that H-scan ultrasound imaging is a new and promising tissue characterization modality. H-scan ultrasound imaging may provide prognostic value when monitoring early tumor response to neoadjuvant treatment. © 2018 by the American Institute of Ultrasound in Medicine.