Priyanka Jha

Optical Imaging of Cellular Immunotherapy against Prostate Cancer

The purpose of this study was to track fluorophore-labeled, tumor-targeted natural killer (NK) cells to human prostate cancer xenografts with optical imaging (OI). NK-92-scFv(MOC31)-zeta cells targeted to the epithelial cell adhesion molecule (EpCAM) antigen on prostate cancer cells and nontargeted NK-92 parental cells were labeled with the near-infrared dye DiD (1,1-dioctadecyl-3,3,3,3-tetramethylindodicarbocyanine). The fluorescence, viability, and cytotoxicity of the labeled cells were evaluated. Subsequently, 12 athymic rats with prostate cancer xenografts underwent OI scans before and up to 24 hours postinjection of DiD-labeled parental NK-92 cells or NK-92-scFv(MOC31)-zeta cells. The tumor fluorescence intensity was measured and compared between pre- and postinjection scans and between both groups using t-tests. OI data were confirmed with fluorescence microscopy. In vitro studies demonstrated a significant increase in the fluorescence of labeled cells compared with unlabeled controls, which persisted over a period of 24 hours without any significant change in the viability. In vivo studies demonstrated a significant increase in tumor fluorescence at 24 hours postinjection of tumor-targeted NK-92-scFv(MOC31)-zeta cells but not parental NK cells. Ex vivo OI scans and fluorescence microscopy confirmed a specific accumulation of NK-92-scFv(MOC31)-zeta cells but not parental NK cells in the tumors. Tumor-targeted NK-92-scFv(MOC31)-zeta cells could be tracked to prostate cancer xenografts with OI.

Radiologic mimics of cirrhosis.

OBJECTIVE The objective of this article is to provide a practical review of the conditions other than cirrhosis that can result in diffuse surface nodularity of the liver or portal hypertension. CONCLUSION Conditions that can mimic cirrhosis on imaging include pseudocirrhosis of treated breast cancer metastases to the liver, fulminant hepatic failure, miliary metastases, sarcoidosis, schistosomiasis, congenital hepatic fibrosis, idiopathic portal hypertension, early primary biliary cirrhosis, chronic Budd-Chiari syndrome, chronic portal vein thrombosis, and nodular regenerative hyperplasia.

Pediatric liver tumors – a pictorial review

Hepatic masses constitute about 5–6% of all intra-abdominal masses in children. The majority of liver tumors in children are malignant; these malignant liver tumors constitute the third most common intra-abdominal malignancy in the pediatric age group after Wilms’ tumor and neuroblastoma. Only about one third of the liver tumors are benign. A differential diagnosis of liver tumors in children can be obtained based on the age of the child, clinical information (in particular AFP) and imaging characteristics. The purpose of this review is to report typical clinical and imaging characteristics of benign and malignant primary liver tumors in children.

Labeling human embryonic stem cell-derived cardiomyocytes with indocyanine green for noninvasive tracking with optical imaging: an FDA-compatible alternative to firefly luciferase.

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) have demonstrated the ability to improve myocardial function following transplantation into an ischemic heart; however, the functional benefits are transient possibly due to poor cell retention. A diagnostic technique that could visualize transplanted hESC-CMs could help to optimize stem cell delivery techniques. Thus, the purpose of this study was to develop a labeling technique for hESCs and hESC-CMs with the FDA-approved contrast agent indocyanine green (ICG) for optical imaging (OI). hESCs were labeled with 0.5, 1.0, 2.0, and 2.5 mg/ml of ICG for 30, 45, and 60 min at 37 degrees C. Longitudinal OI studies were performed with both hESCs and hESC-CMs. The expression of surface proteins was assessed with immunofluorescent staining. hESCs labeled with 2 mg ICG/ml for 60 min achieved maximum fluorescence. Longitudinal studies revealed that the fluorescent signal was equivalent to controls at 120 h postlabeling. The fluorescence signal of hESCs and hESC-CMs at 1, 24, and 48 h was significantly higher compared to precontrast data (p < 0.05). Immunocytochemistry revealed retention of cell-specific surface and nuclear markers postlabeling. These data demonstrate that hESCs and hESC-CMs labeled with ICG show a significant fluorescence up to 48 h and can be visualized with OI. The labeling procedure does not impair the viability or functional integrity of the cells. The technique may be useful for assessing different delivery routes in order to improve the engraftment of transplanted hESC-CMs or other stem cell progenitors.

Monitoring of natural killer cell immunotherapy using noninvasive imaging modalities.

Cancer immunotherapies can be guided by cellular imaging techniques, which can identify the presence or absence of immune cell accumulation in the tumor tissue in vivo and in real time. This review summarizes various new and evolving imaging techniques employed for tracking and monitoring of adoptive natural killer cell immunotherapies.

Somatic Differentiation and MR Imaging of Magnetically Labeled Human Embryonic Stem Cells

Magnetic resonance (MR) imaging of superparamagnetic iron oxide (SPIO)-labeled stem cells offers a non-invasive evaluation of stem cell engraftment in host organs. Excessive cellular iron load from SPIO labeling, however, impairs stem cell differentiation. The purpose of this study was to magnetically label human embryonic stem cells (hESCs) via a reduced exposure protocol that maintains a significant MR signal and no significant impairment to cellular pluripotency or differentiation potential. hESCs were labeled by simple incubation with Food and Drug Administration-approved ferumoxides, using concentrations of 50–200 μg Fe/ml and incubation times of 3–24 h. The most reduced exposure labeling protocol that still provided a significant MR signal comparable to accepted labeling protocols was selected for subsequent studies. Labeled hESCs were compared to unlabeled controls for differences in pluripotency as studied by fluorescence staining for SSEA-1, SSEA-4, TRA-60, and TRA-81 and in differentiation capacity as studied by quantitative real-time PCR for hOCT4, hACTC1, hSOX1, and hAFP after differentiation into embryoid bodies (EBs). Subsequent MR and microscopy imaging were performed to evaluate for cellular iron distribution and long-term persistence of the label. An incubation concentration of 50 μg Fe/ml and incubation time of 3 h demonstrated a significantly reduced exposure protocol that yielded an intracellular iron uptake of 4.50 ± 0.27 pg, an iron content comparable to currently accepted SPIO labeling protocols. Labeled and unlabeled hESCs showed no difference in pluripotency or differentiation capacity. Ferumoxide-labeled hESCs demonstrated persistent MR contrast effects as embryoid bodies for 21 days. Electron microscopy confirmed persistent lysosomal storage of iron oxide particles in EBs up to 9 days, while additional microscopy confirmed the iron distribution within single and multiple EBs. Labeling hESCs with ferumoxides by this tailored protocol reduces exposure of cells to the labeling agent while allowing for long-term visualization with MR imaging and the retention of cellular pluripotency and differentiation potential.

Endorectal MRI and MR spectroscopic imaging of prostate cancer: developing selection criteria for MR-guided focal therapy.

To investigate criteria that can identify dominant treatable prostate cancer foci with high certainty at endorectal magnetic resonance imaging (MRI) and MR spectroscopic (MRS) imaging, and thus facilitate selection of patients who are radiological candidates for MR‐guided focal therapy.

Congenital tracheobiliary fistula diagnosed with contrast-enhanced CT and 3-D reformation

Congenital tracheobiliary fistula (CTBF) is a rare malformation. So far 24 cases have been reported in the English language literature. The imaging techniques used in diagnosis have been bronchography, fistulography, cholangiography, hepatobiliary nuclear imaging and MRI. We report a newborn patient who presented with right lung consolidation and biliptysis. The radiographic diagnosis of tracheobiliary fistula was made on multidetector CT scan of the chest and abdomen. Multiple 3-D volume-rendered reformations were performed. An abnormal air-filled tract was seen connecting the posteroinferior aspect of the carina and left biliary system, which was successfully treated surgically.

Optimizing bone surveys performed for suspected non-accidental trauma with attention to maximizing diagnostic yield while minimizing radiation exposure: utility of pelvic and lateral radiographs

BackgroundSkeletal surveys for non-accidental trauma (NAT) include lateral spinal and pelvic views, which have a significant radiation dose.ObjectiveTo determine whether pelvic and lateral spinal radiographs should routinely be performed during initial bone surveys for suspected NAT.Materials and methodsThe radiology database was queried for the period May 2005 to May 2011 using CPT codes for skeletal surveys for suspected NAT. Studies performed for skeletal dysplasia and follow-up surveys were excluded. Initial skeletal surveys were reviewed to identify fractures present, including those identified only on lateral spinal and/or pelvic radiographs. Clinical information and MR imaging was reviewed for the single patient with vertebral compression deformities.ResultsOf the 530 children, 223 (42.1%) had rib and extremity fractures suspicious for NAT. No fractures were identified solely on pelvic radiographs. Only one child (<0.2%) had vertebral compression deformities identified on a lateral spinal radiograph. This infant had rib and extremity fractures and was clinically paraplegic. MR imaging confirmed the vertebral body fractures.ConclusionSince no fractures were identified solely on pelvic radiographs and on lateral spinal radiographs in children without evidence of NAT, nor in nearly all with evidence of NAT, inclusion of these views in the initial evaluation of children for suspected NAT may not be warranted.

Feasibility of Antegrade Contrast-enhanced US Nephrostograms to Evaluate Ureteral Patency

Purpose To demonstrate the feasibility of contrast material-enhanced ulrasonographic (US) nephrostograms to assess ureteral patency after percutaneous nephrolithotomy (PCNL) in this proof-of-concept study. Materials and Methods For this HIPAA-compliant, institutional review board-approved prospective blinded pilot study, patients undergoing PCNL provided consent to undergo contrast-enhanced US and fluoroscopic nephrostograms on postoperative day 1. For contrast-enhanced US, 1.5 mL of Optison (GE Healthcare, Oslo, Norway) microbubble contrast agent solution (perflutren protein-type A microspheres) was injected via the nephrostomy tube. Unobstructed antegrade ureteral flow was defined by the presence of contrast material in the bladder. Contrast-enhanced US results were compared against those of fluoroscopic nephrostograms for concordance. Results Ten studies were performed in nine patients (four women, five men). Contrast-enhanced US demonstrated ureteral patency in eight studies and obstruction in two. One patient underwent two studies, one showing obstruction and the second showing patency. Concordance between US and fluoroscopic assessments of ureteral patency was evaluated by using a Clopper-Pearson exact binomial test. These results were perfectly concordant with fluoroscopic nephrostogram results, with a 95% confidence interval of 69.2% and 100%. No complications or adverse events related to contrast-enhanced US occurred. Conclusion Contrast-enhanced US nephrostograms are simple to perform and are capable of demonstrating both patency and obstruction of the ureter. The perfect concordance with fluoroscopic results across 10 studies demonstrated here is not sufficient to establish diagnostic accuracy of this technique, but motivates further, larger scale investigation. If subsequent larger studies confirm these preliminary results, contrast-enhanced US may provide a safer, more convenient way to evaluate ureteral patency than fluoroscopy.