Bio

Clinical Focus


  • Fellow

Honors & Awards


  • Elliott C. Lasser Award for Excellence in Research during radiology residency (2014-18), UCSD Alumni Society, San Diego, USA (2018)
  • Cover image and Featured article in the April 2018 issue of MRM, Magnetic Resonance in Medicine (MRM), ISMRM journal (2018)
  • Travel Student Award, Annual Meeting of the Radiological Society of North America (RSNA), Chicago, USA (2016)
  • Invitation for publication in Radiographics for ?Fetal Cardiac Screening Sonography: Methodology", Annual Meeting of the Radiological Society of North America (RSNA), Chicago, USA (2015)
  • Certificate of Merit Award for RSNA poster- ?Fetal Cardiac Screening Sonography: Methodology", Annual Meeting of the Radiological Society of North America (RSNA), Chicago, USA (2015)
  • Resident Program invitation to participate as a resident/fellow, Society of Radiologists in Ultrasound (SRU) (2015)
  • Finalist for Alexander R Margulis Award for Scientific Excellence, Annual Meeting of the Radiological Society of North America (RSNA), Chicago, USA (2014)
  • Travel Stipend, World Molecular Imaging Congress, San Diego, CA, USA (2011)
  • Trainee research prize, Fellow, Annual Meeting of the Radiological Society of North America (RSNA), Chicago (2013)
  • Travel Stipend, World Molecular Imaging Congress, Dublin, Ireland (2012)

Professional Education


  • MD, Stanford University, Body Imaging Fellow (2019)
  • MD, University of California, San Diego, Radiology Residency (2018)
  • Post-doctoral fellow, Stanford University, MR stem cell tracking (2010)
  • Medical Rotation, Tulane University, Acute care surgery (2009)
  • Medical rotation, Tulane University, Internal medicine- Gastroenterology & Endocrinology (2009)
  • Research assosciate, University of California, San Francisco, Radiology (2009)
  • Medical Rotation, University of California, San Francisco, Radiology (2009)

Research & Scholarship

Current Research and Scholarly Interests


My research interest focuses on cellular imaging and MR imaging. My current projects involve evaluations of a FDA approved iron oxide contrast agent, ferumoxytol, for in vivo tracking of stem cell transplants and immune cells. The goal of these cellular imaging techniques is to non-invasively monitor stem cell mediated tissue regeneration and related immune rejection processes. Keeping the translational potential of this agent in mind, we ultimately aim to translate these novel technologies to the clinic.

Lab Affiliations


Publications

All Publications


  • Evaluation of Virtual Reality for Detection of Lung Nodules on Computed Tomography. Tomography (Ann Arbor, Mich.) Nguyen, B. J., Khurana, A., Bagley, B., Yen, A., Brown, R. K., Stojanovska, J., Cline, M., Goodsitt, M., Obrzut, S. 2018; 4 (4): 204?8

    Abstract

    Virtual reality (VR) systems can offer benefits of improved ergonomics, but their resolution may currently be limited for the detection of small features. For detection of lung nodules, we compared the performance of VR versus standard picture archiving and communication system (PACS) monitor. Four radiologists and 1 novice radiologist reviewed axial computed tomography (CTs) of the thorax using standard PACS monitors (SM) and a VR system (HTC Vive, HTC). In this study, 3 radiologists evaluated axial lung-window CT images of a Lungman phantom. One radiologist and the novice radiologist reviewed axial lung-window patient CT thoracic images (32 patients). This HIPAA-compliant study was approved by the institutional review board. Detection of 227 lung nodules on patient CTs did not result in different sensitivity with SM compared with VR. Detection of 23 simulated Lungman phantom lung nodules on CT with SM resulted in statistically greater sensitivity (78.3%) than with VR (52.2%, P = .041) for 1 of 3 radiologists. The trend was similar but not significant for the other radiologists. There was no significant difference in the time spent by readers reviewing CT images with VR versus SM. These findings indicate that performance of a commercially available VR system for detection of lung nodules may be similar to traditional radiology monitors for assessment of small lung nodules on CTs of the thorax for most radiologists. These results, along with the potential of improving ergonomics for radiologists, are promising for the future development of VR in diagnostic radiology.

    View details for DOI 10.18383/j.tom.2018.00053

    View details for PubMedID 30588506

  • Tumor Formation of Adult Stem Cell Transplants in Rodent Arthritic Joints. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging Chapelin, F., Khurana, A., Moneeb, M., Gray Hazard, F. K., Chan, C. F., Nejadnik, H., Gratzinger, D., Messing, S., Erdmann, J., Gaur, A., Daldrup-Link, H. E. 2018

    Abstract

    While imaging matrix-associated stem cell transplants aimed for cartilage repair in a rodent arthritis model, we noticed that some transplants formed locally destructive tumors. The purpose of this study was to determine the cause for this tumor formation in order to avoid this complication for future transplants.Adipose-derived stem cells (ADSC) isolated from subcutaneous adipose tissue were implanted into 24 osteochondral defects of the distal femur in ten athymic rats and two immunocompetent control rats. All transplants underwent serial magnetic resonance imaging (MRI) up to 6 weeks post-transplantation to monitor joint defect repair. Nine transplants showed an increasing size over time that caused local bone destruction (group 1), while 11 transplants in athymic rats (group 2) and 4 transplants in immunocompetent rats did not. We compared the ADSC implant size and growth rate on MR images, macroscopic features, histopathologic features, surface markers, and karyotypes of these presumed neoplastic transplants with non-neoplastic ADSC transplants.Implants in group 1 showed a significantly increased two-dimensional area at week 2 (p?=?0.0092), 4 (p?=?0.003), and 6 (p?=?0.0205) compared to week 0, as determined by MRI. Histopathological correlations confirmed neoplastic features in group 1 with significantly increased size, cellularity, mitoses, and cytological atypia compared to group 2. Six transplants in group 1 were identified as malignant chondrosarcomas and three transplants as fibromyxoid sarcomas. Transplants in group 2 and immunocompetent controls exhibited normal cartilage features. Both groups showed a normal ADSC phenotype; however, neoplastic ADSC demonstrated a mixed population of diploid and tetraploid cells without genetic imbalance.ADSC transplants can form tumors in vivo. Preventive actions to avoid in vivo tumor formations may include karyotyping of culture-expanded ADSC before transplantation. In addition, serial imaging of ADSC transplants in vivo may enable early detection of abnormally proliferating cell transplants.

    View details for DOI 10.1007/s11307-018-1218-7

    View details for PubMedID 29869062

  • Visualization of macrophage recruitment in head and neck carcinoma model using fluorine-19 magnetic resonance imaging. Magnetic resonance in medicine Khurana, A., Chapelin, F., Xu, H., Acevedo, J. R., Molinolo, A., Nguyen, Q., Ahrens, E. T. 2018; 79 (4): 1972?80

    Abstract

    To evaluate the role of infiltrating macrophages in murine models of single and double mutation head and neck tumors using a novel fluorine-19 (19 F) MRI technology.Tumor cell lines single-hit/SCC4 or double-hit/Cal27, with mutations of TP53 and TP53 & FHIT, respectively, were injected bilaterally into the flanks of (n?=?10) female mice. With tumors established, perfluorocarbon nanoemulsion was injected intravenously, which labels in situ predominantly monocytes and macrophages. Longitudinal spin density-weighted 19 F MRI data enabled quantification of the macrophage burden in tumor and surrounding tissue.The average number of 19 F atoms within the tumors was twice as high in the Cal27 group compared with SCC4 (3.9?×?1019 and 2.0?×?101919 F/tumor, respectively; P?=?0.0034) two days after contrast injection, signifying increased tumor-associated macrophages in double-hit tumors. The difference was still significant 10 days after injection. Histology stains correlated with in vivo results, exhibiting numerous perfluorocarbon-labeled macrophages in double-hit tumors and to a lesser extent in single-hit tumors.This study helps to establish 19 F MRI as a method for quantifying immune cells in the tumor microenvironment, allowing distinction between double and single-hit head and neck tumors. This technique would be extremely valuable in the clinic for pretreatment planning, prognostics, and post-treatment surveillance. Magn Reson Med 79:1972-1980, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

    View details for DOI 10.1002/mrm.26854

    View details for PubMedID 28748562

    View details for PubMedCentralID PMC5807236

  • Luteoma of Pregnancy ULTRASOUND QUARTERLY Khurana, A., O'Boyle, M. 2017; 33 (1): 90-92

    View details for DOI 10.1097/RUQ.0000000000000255

    View details for Web of Science ID 000397602900021

    View details for PubMedID 28081022

  • Detection of Stem Cell Transplant Rejection with Ferumoxytol MR Imaging: Correlation of MR Imaging Findings with Those at Intravital Microscopy. Radiology Daldrup-Link, H. E., Chan, C., Lenkov, O., Taghavigarmestani, S., Nazekati, T., Nejadnik, H., Chapelin, F., Khurana, A., Tong, X., Yang, F., Pisani, L., Longaker, M., Gambhir, S. S. 2017: 161139-?

    Abstract

    Purpose To determine whether endogenous labeling of macrophages with clinically applicable nanoparticles enables noninvasive detection of innate immune responses to stem cell transplants with magnetic resonance (MR) imaging. Materials and Methods Work with human stem cells was approved by the institutional review board and the stem cell research oversight committee, and animal experiments were approved by the administrative panel on laboratory animal care. Nine immunocompetent Sprague-Dawley rats received intravenous injection of ferumoxytol, and 18 Jax C57BL/6-Tg (Csf1r-EGFP-NGFR/FKBP1A/TNFRSF6) 2Bck/J mice received rhodamine-conjugated ferumoxytol. Then, 48 hours later, immune-matched or mismatched stem cells were implanted into osteochondral defects of the knee joints of experimental rats and calvarial defects of Jax mice. All animals underwent serial MR imaging and intravital microscopy (IVM) up to 4 weeks after surgery. Macrophages of Jax C57BL/6-Tg (Csf1r-EGFP-NGFR/FKBP1A/TNFRSF6) 2Bck/J mice express enhanced green fluorescent protein (GFP), which enables in vivo correlation of ferumoxytol enhancement at MR imaging with macrophage quantities at IVM. All quantitative data were compared between experimental groups by using a mixed linear model and t tests. Results Immune-mismatched stem cell implants demonstrated stronger ferumoxytol enhancement than did matched stem cell implants. At 4 weeks, T2 values of mismatched implants were significantly lower than those of matched implants in osteochondral defects of female rats (mean, 10.72 msec for human stem cells and 11.55 msec for male rat stem cells vs 15.45 msec for sex-matched rat stem cells; P = .02 and P = .04, respectively) and calvarial defects of recipient mice (mean, 21.7 msec vs 27.1 msec, respectively; P = .0444). This corresponded to increased recruitment of enhanced GFP- and rhodamine-ferumoxytol-positive macrophages into stem cell transplants, as visualized with IVM and histopathologic examination. Conclusion Endogenous labeling of macrophages with ferumoxytol enables noninvasive detection of innate immune responses to stem cell transplants with MR imaging. (©) RSNA, 2017 Online supplemental material is available for this article.

    View details for DOI 10.1148/radiol.2017161139

    View details for PubMedID 28128708

  • Fetal Cardiac Screening Sonography: Methodology: Women's Imaging. Radiographics Khurana, A., Burt, A., Beck, G., Anton, T., Perez, M., Levy, D., Pretorius, D. 2017; 37 (1): 360-361

    View details for DOI 10.1148/rg.2017160072

    View details for PubMedID 28076004

  • Science to Practice: Can MR Imaging Cell Tracking of Macrophage Infiltration Be Used as a Predictive Imaging Biomarker for Transplanted Stem Cell Rejection? Radiology Bulte, J. W. 2017; 284 (2): 307?9

    Abstract

    Ferumoxytol-enhanced magnetic resonance (MR) imaging of donor-matched and mismatched stem cell transplants demonstrated decreased signal intensity not only for a xenogeneic mismatch in species but, surprisingly, also for a syngeneic mismatch in sex. MR imaging findings were corroborated with intravital fluorescence microscopy (IVM), where nearly 90% of all ferumoxytol-containing cells were found to be macrophages. Hence, MR imaging cell tracking of infiltrating macrophages may have predictive value in determining whether transplanted stem cell rejection will occur.

    View details for DOI 10.1148/radiol.2017170536

    View details for PubMedID 28723288

  • Ionising radiation-free whole-body MRI versus (18)F-fluorodeoxyglucose PET/CT scans for children and young adults with cancer: a prospective, non-randomised, single-centre study. lancet oncology Klenk, C., Gawande, R., Uslu, L., Khurana, A., Qiu, D., Quon, A., Donig, J., Rosenberg, J., Luna-Fineman, S., Moseley, M., Daldrup-Link, H. E. 2014; 15 (3): 275-285

    Abstract

    Imaging tests are essential for staging of children with cancer. However, CT and radiotracer-based imaging procedures are associated with substantial exposure to ionising radiation and risk of secondary cancer development later in life. Our aim was to create a highly effective, clinically feasible, ionising radiation-free staging method based on whole-body diffusion-weighted MRI and the iron supplement ferumoxytol, used off-label as a contrast agent.We compared whole-body diffusion-weighted MRI with standard clinical (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT scans in children and young adults with malignant lymphomas and sarcomas. Whole-body diffusion-weighted magnetic resonance images were generated by coregistration of colour-encoded ferumoxytol-enhanced whole-body diffusion-weighted MRI scans for tumour detection with ferumoxytol-enhanced T1-weighted MRI scans for anatomical orientation, similar to the concept of integrated (18)F-FDG PET/CT scans. Tumour staging results were compared using Cohen's ? statistics. Histopathology and follow-up imaging served as the standard of reference. Data was assessed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01542879.22 of 23 recruited patients were analysed because one patient discontinued before completion of the whole-body scan. Mean exposure to ionising radiation was 12·5 mSv (SD 4·1) for (18)F-FDG PET/CT compared with zero for whole-body diffusion-weighted MRI. (18)F-FDG PET/CT detected 163 of 174 malignant lesions at 1325 anatomical regions and whole-body diffusion-weighted MRI detected 158. Comparing (18)F-FDG PET/CT to whole-body diffusion-weighted MRI, sensitivities were 93·7% (95% CI 89·0-96·8) versus 90·8% (85·5-94·7); specificities 97·7% (95% CI 96·7-98·5) versus 99·5% (98·9-99·8); and diagnostic accuracies 97·2% (93·6-99·4) versus 98·3% (97·4-99·2). Tumour staging results showed very good agreement between both imaging modalities with a ? of 0·93 (0·81-1·00). No adverse events after administration of ferumoxytol were recorded.Ferumoxytol-enhanced whole-body diffusion-weighted MRI could be an alternative to (18)F-FDG PET/CT for staging of children and young adults with cancer that is free of ionising radiation. This new imaging test might help to prevent long-term side-effects from radiographic staging procedures.Thrasher Research Fund and Clinical Health Research Institute at Stanford University.

    View details for DOI 10.1016/S1470-2045(14)70021-X

    View details for PubMedID 24559803

  • Ferumoxytol: a new, clinically applicable label for stem-cell tracking in arthritic joints with MRI. Nanomedicine Khurana, A., Nejadnik, H., Chapelin, F., Lenkov, O., Gawande, R., Lee, S., Gupta, S. N., Aflakian, N., Derugin, N., Messing, S., Lin, G., Lue, T. F., Pisani, L., Daldrup-Link, H. E. 2013; 8 (12): 1969-1983

    Abstract

    Aim: To develop a clinically applicable MRI technique for tracking stem cells in matrix-associated stem-cell implants, using the US FDA-approved iron supplement ferumoxytol. Materials & methods: Ferumoxytol-labeling of adipose-derived stem cells (ADSCs) was optimized in vitro. A total of 11 rats with osteochondral defects of both femurs were implanted with ferumoxytol- or ferumoxides-labeled or unlabeled ADSCs, and underwent MRI up to 4 weeks post matrix-associated stem-cell implant. The signal-to-noise ratio of different matrix-associated stem-cell implant was compared with t-tests and correlated with histopathology. Results: An incubation concentration of 500 µg iron/ml ferumoxytol and 10 µg/ml protamine sulfate led to significant cellular iron uptake, T2 signal effects and unimpaired ADSC viability. In vivo, ferumoxytol- and ferumoxides-labeled ADSCs demonstrated significantly lower signal-to-noise ratio values compared with unlabeled controls (p < 0.01). Histopathology confirmed engraftment of labeled ADSCs, with slow dilution of the iron label over time. Conclusion: Ferumoxytol can be used for in vivo tracking of stem cells with MRI. Original submitted 28 February 2012; Revised submitted 8 November 2012.

    View details for DOI 10.2217/nnm.12.198

    View details for PubMedID 23534832

  • Iron Administration before Stem Cell Harvest Enables MR Imaging Tracking after Transplantation. Radiology Khurana, A., Chapelin, F., Beck, G., Lenkov, O. D., Donig, J., Nejadnik, H., Messing, S., Derugin, N., Chan, R. C., Gaur, A., Sennino, B., McDonald, D. M., Kempen, P. J., Tikhomirov, G. A., Rao, J., Daldrup-Link, H. E. 2013; 269 (1): 186-197

    Abstract

    Purpose:To determine whether intravenous ferumoxytol can be used to effectively label mesenchymal stem cells (MSCs) in vivo and can be used for tracking of stem cell transplants.Materials and Methods:This study was approved by the institutional animal care and use committee. Sprague-Dawley rats (6-8 weeks old) were injected with ferumoxytol 48 hours prior to extraction of MSCs from bone marrow. Ferumoxytol uptake by these MSCs was evaluated with fluorescence, confocal, and electron microscopy and compared with results of traditional ex vivo-labeling procedures. The in vivo-labeled cells were subsequently transplanted in osteochondral defects of 14 knees of seven athymic rats and were evaluated with magnetic resonance (MR) imaging up to 4 weeks after transplantation. T2 relaxation times of in vivo-labeled MSC transplants and unlabeled control transplants were compared by using t tests. MR data were correlated with histopathologic results.Results:In vivo-labeled MSCs demonstrated significantly higher ferumoxytol uptake compared with ex vivo-labeled cells. With electron microscopy, iron oxide nanoparticles were localized in secondary lysosomes. In vivo-labeled cells demonstrated significant T2 shortening effects in vitro and in vivo when they were compared with unlabeled control cells (T2 in vivo, 15.4 vs 24.4 msec; P < .05) and could be tracked in osteochondral defects for 4 weeks. Histologic examination confirmed the presence of iron in labeled transplants and defect remodeling.Conclusion:Intravenous ferumoxytol can be used to effectively label MSCs in vivo and can be used for tracking of stem cell transplants with MR imaging. This method eliminates risks of contamination and biologic alteration of MSCs associated with ex vivo-labeling procedures.© RSNA, 2013Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130858/-/DC1.

    View details for DOI 10.1148/radiol.13130858

    View details for PubMedID 23850832

  • Science to Practice: Can Stem Cells Be Labeled Inside the Body Instead of Outside? RADIOLOGY Bulte, J. W. 2013; 269 (1): 1-3

    Abstract

    Instead of conventional labeling ex vivo in cell culture, mesenchymal stem cells (MSCs) were labeled in vivo with intravenous injection of ferumoxytol (Feraheme; AMAG Pharmaceuticals, Lexington, Mass), a Food and Drug Administration (FDA)-approved intravenous iron supplement. After their isolation and processing from bone marrow, the same MSCs were injected in rats with an osteochondral defect, allowing MR monitoring of their engraftment for at least 4 weeks. This straightforward labeling approach, avoiding several regulatory issues, may accelerate clinical translation of magnetic resonance (MR) imaging for stem cell tracking.

    View details for DOI 10.1148/radiol.13131753

    View details for Web of Science ID 000325000700001

    View details for PubMedID 24062557

    View details for PubMedCentralID PMC5432207

  • Role of diffusion-weighted imaging in differentiating benign and malignant pediatric abdominal tumors. Pediatric radiology Gawande, R. S., Gonzalez, G., Messing, S., Khurana, A., Daldrup-Link, H. E. 2013; 43 (7): 836-845

    Abstract

    BACKGROUND: Solid malignant tumors are more highly cellular than benign lesions and hence have a restricted diffusion of water molecules. OBJECTIVE: To evaluate whether diffusion-weighted MR imaging (DWI) can differentiate between benign and malignant pediatric abdominal tumors. MATERIALS AND METHODS: We retrospectively analyzed DWI scans of 68 consecutive children with 39 benign and 34 malignant abdominal masses. To calculate the apparent diffusion coefficient (ADC) maps and ADC values, we used 1.5-T sequences at TR/TE/b-value of 5,250-7,500/54-64/b?=?0, 500 and 3-T sequences at 3,500-4,000/66-73/b?=?0, 500, 800. ADC values were compared between benign and malignant and between data derived at 1.5 tesla (T) and at 3 tesla magnetic field strength, using the Mann-Whitney-Wilcoxon test, ANOVA and a receiver operating curve (ROC) analysis. RESULTS: There was no significant difference in ADC values obtained at 1.5 T and 3 T (P?=?0.962). Mean ADC values (× 10(-3)?mm(2)/s) were 1.07 for solid malignant tumors, 1.6 for solid benign tumors, 2.9 for necrotic portions of malignant tumors and 3.1 for cystic benign lesions. The differences between malignant and benign solid tumors were statistically significant (P?=?0.000025). ROC analysis revealed an optimal cut-off ADC value for differentiating malignant and benign solid tumors as 1.29 with excellent inter-observer reliability (alpha score 0.88). CONCLUSION: DWI scans and ADC values can contribute to distinguishing between benign and malignant pediatric abdominal tumors.

    View details for DOI 10.1007/s00247-013-2626-0

    View details for PubMedID 23666206

  • Comparison of the diagnostic value of MR imaging and ophthalmoscopy for the staging of retinoblastoma EUROPEAN RADIOLOGY Khurana, A., Eisenhut, C. A., Wan, W., Ebrahimi, K. B., Patel, C., O'Brien, J. M., Yeom, K., Daldrup-Link, H. E. 2013; 23 (5): 1271-1280

    Abstract

    To compare the diagnostic value of magnetic resonance (MR) imaging and ophthalmoscopy for staging of retinoblastoma.MR and ophthalmoscopic images of 36 patients who underwent enucleation were evaluated retrospectively following institutional review board approval. Histopathology being the standard of reference, the sensitivity and specificity of both diagnostic modalities were compared regarding growth pattern, iris neoangiogenesis, retinal detachment, vitreous seeds and optic nerve invasion. Data were analysed via McNemar's test.Both investigations showed no significant difference in accuracy for the detection of different tumour growth patterns (P = 0.80). Vitreous seeding detection was superior by ophthalmoscopy (P < 0.001). For prelaminar optic nerve invasion, MR imaging showed similar sensitivity as ophthalmoscopy but increased specificity of 40 % (CI 0.12-0.74) vs. 20 % (0.03-0.56). MR detected optic nerve involvement past the lamina cribrosa with a sensitivity of 80 % (0.28-0.99) and a specificity of 74 % (0.55-0.88). The absence of optic nerve enhancement excluded histopathological infiltration, but the presence of optic nerve enhancement included a high number of false positives (22-24 %).Ophthalmoscopy remains the method of choice for determining extent within the globe while MR imaging is useful for evaluating extraocular tumour extension. Thus, both have their own strengths and contribute uniquely to the staging of retinoblastoma.? Ophthalmoscopy: method of choice for determining extent of retinoblastoma within the globe. ? MR imaging provides optimal evaluation of extrascleral and extraocular tumour extension. ? Positive enhancement of the optic nerve on MRI does not necessarily indicate involvement.

    View details for DOI 10.1007/s00330-012-2707-8

    View details for Web of Science ID 000317427500015

    View details for PubMedID 23160663

  • Intravenous Ferumoxytol Allows Noninvasive MR Imaging Monitoring of Macrophage Migration into Stem Cell Transplants RADIOLOGY Khurana, A., Nejadnik, H., Gawande, R., Lin, G., Lee, S., Messing, S., Castaneda, R., Derugin, N., Pisani, L., Lue, T. F., Daldrup-Link, H. E. 2012; 264 (3): 803-811

    Abstract

    To develop a clinically applicable imaging technique for monitoring differential migration of macrophages into viable and apoptotic matrix-associated stem cell implants (MASIs) in arthritic knee joints.With institutional animal care and use committee approval, six athymic rats were injected with intravenous ferumoxytol (0.5 mmol iron per kilogram of body weight) to preload macrophages of the reticuloendothelial system with iron oxide nanoparticles. Forty-eight hours later, all animals received MASIs of viable adipose-derived stem cells (ADSCs) in an osteochondral defect of the right femur and mitomycin-pretreated apoptotic ADSCs in an osteochondral defect of the left femur. One additional control animal each received intravenous ferumoxytol and bilateral scaffold-only implants (without cells) or bilateral MASIs without prior ferumoxytol injection. All knees were imaged with a 7.0-T magnetic resonance (MR) imaging unit with T2-weighted fast spin-echo sequences immediately after, as well as 2 and 4 weeks after, matrix-associated stem cell implantation. Signal-to-noise ratios (SNRs) of viable and apoptotic MASIs were compared by using a linear mixed-effects model. MR imaging data were correlated with histopathologic findings.All ADSC implants showed a slowly decreasing T2 signal over 4 weeks after matrix-associated stem cell implantation. SNRs decreased significantly over time for the apoptotic implants (SNRs on the day of matrix-associated stem cell implantation, 2 weeks after the procedure, and 4 weeks after the procedure were 16.9, 10.9, and 6.7, respectively; P = .0004) but not for the viable implants (SNRs on the day of matrix-associated stem cell implantation, 2 weeks after the procedure, and 4 weeks after the procedure were 17.7, 16.2, and 15.7, respectively; P = .2218). At 4 weeks after matrix-associated stem cell implantation, SNRs of apoptotic ADSCs were significantly lower than those of viable ADSCs (mean, 6.7 vs 15.7; P = .0013). This corresponded to differential migration of iron-loaded macrophages into MASIs.Iron oxide loading of macrophages in the reticuloendothelial system by means of intravenous ferumoxytol injection can be utilized to monitor differential migration of bone marrow macrophages into viable and apoptotic MASIs in a rat model.

    View details for DOI 10.1148/radiol.12112393

    View details for Web of Science ID 000308645500022

    View details for PubMedID 22820731

    View details for PubMedCentralID PMC3426856

  • Science to Practice: Can Macrophage Infiltration Serve as a Surrogate Marker for Stem Cell Viability? RADIOLOGY Bulte, J. W. 2012; 264 (3): 619-620

    Abstract

    Following in vivo prelabeling of host macrophages with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, it was shown that their magnetic resonance (MR) imaging?visible migration into knee implants of scaffolded adipose-derived stem cells (ADSCs) undergoing apoptosis can serve as a surrogate marker of stem cell death.

    View details for Web of Science ID 000308645500001

    View details for PubMedID 22919033

  • A photonic crystal cavity-optical fiber tip nanoparticle sensor for biomedical applications APPLIED PHYSICS LETTERS Shambat, G., Kothapalli, S. R., Khurana, A., Provine, J., Sarmiento, T., Cheng, K., Cheng, Z., Harris, J., Daldrup-Link, H., Gambhir, S. S., Vuckovic, J. 2012; 100 (21)

    View details for DOI 10.1063/1.4719520

    View details for Web of Science ID 000304489900085

  • Magnetic Resonance Imaging of Ferumoxide-Labeled Mesenchymal Stem Cells in Cartilage Defects: In Vitro and In Vivo Investigations MOLECULAR IMAGING Henning, T. D., Gawande, R., Khurana, A., Tavri, S., Mandrussow, L., Golovko, D., Horvai, A., Sennino, B., McDonald, D., Meier, R., Wendland, M., Derugin, N., Link, T. M., Daldrup-Link, H. E. 2012; 11 (3): 197-209

    Abstract

    The purpose of this study was to (1) compare three different techniques for ferumoxide labeling of mesenchymal stem cells (MSCs), (2) evaluate if ferumoxide labeling allows in vivo tracking of matrix-associated stem cell implants (MASIs) in an animal model, and (3) compare the magnetic resonance imaging (MRI) characteristics of ferumoxide-labeled viable and apoptotic MSCs. MSCs labeled with ferumoxide by simple incubation, protamine transfection, or Lipofectin transfection were evaluated with MRI and histopathology. Ferumoxide-labeled and unlabeled viable and apoptotic MSCs in osteochondral defects of rat knee joints were evaluated over 12 weeks with MRI. Signal to noise ratios (SNRs) of viable and apoptotic labeled MASIs were tested for significant differences using t-tests. A simple incubation labeling protocol demonstrated the best compromise between significant magnetic resonance signal effects and preserved cell viability and potential for immediate clinical translation. Labeled viable and apoptotic MASIs did not show significant differences in SNR. Labeled viable but not apoptotic MSCs demonstrated an increasing area of T2 signal loss over time, which correlated to stem cell proliferation at the transplantation site. Histopathology confirmed successful engraftment of viable MSCs. The engraftment of iron oxide-labeled MASIs by simple incubation can be monitored over several weeks with MRI. Viable and apoptotic MASIs can be distinguished via imaging signs of cell proliferation at the transplantation site.

    View details for DOI 10.2310/7290.2011.00040

    View details for Web of Science ID 000307646000003

    View details for PubMedID 22554484

  • Differentiation of Normal Thymus from Anterior Mediastinal Lymphoma and Lymphoma Recurrence at Pediatric PET/CT RADIOLOGY Gawande, R. S., Khurana, A., Messing, S., Zhang, D., Castaneda, R. T., Goldsby, R. E., Hawkins, R. A., Daldrup-Link, H. E. 2012; 262 (2): 613-622

    Abstract

    To evaluate the role of positron emission tomography (PET)/computed tomography (CT) in the differentiation of normal thymus from mediastinal lymphoma and lymphoma recurrence in pediatric patients.The study was approved by the institutional review board, and informed consent was waived. The study was HIPAA compliant. Two hundred eighty-two fluorine 18 fluorodeoxyglucose PET/CT studies in 75 pediatric oncology patients were reviewed retrospectively. Patients were divided into four groups: anterior mediastinal lymphoma (group A, n=16), anterior mediastinal lymphoma with subsequent recurrence (group B, n=5), lymphoma outside the mediastinum (group C, n=16), and other malignant tumors outside the thymus (group D, n=38). Analyses included measurements of the maximum anteroposterior and transverse dimensions of the anterior mediastinal mass or thymus on axial CT images and measurements of maximum standardized uptake values of anterior mediastinal mass, thymus (SUVt), and bone marrow at the level of the fifth lumbar vertebra (SUVb) on PET images. Quantitative parameters were compared by using an analysis of variance test.Mean prechemotherapy SUVt was 4.82 for group A, 8.45 for group B, 2.00 for group C, and 2.09 for group D. Mean postchemotherapy SUVt for group B was 4.74. Thymic rebound (mean SUVt, 2.89) was seen in 44% of patients at a mean interval of 10 months from the end of chemotherapy. The differences between prechemotherapy SUVt of mediastinal lymphoma and normal thymus and postchemotherapy SUVt of lymphoma recurrence and thymic rebound were highly significant (P<.001).SUVt is a sensitive predictor for differentiation of normal thymus or thymic rebound from mediastinal lymphoma. SUVt of 3.4 or higher is a strong predictor of mediastinal lymphoma.

    View details for DOI 10.1148/radiol.11110715

    View details for Web of Science ID 000300300200029

    View details for PubMedID 22157202

  • A photonic crystal cavity-optical fiber tip nanoparticle sensor for biomedical applications. Applied Physics Letters Shambat G, Kothapalli SR, Khurana A, Provine J, Sarmiento T, Cheng K, Cheng Z, Harris J, Daldrup-Link H, Gambhir SS, Vu&#269;kovi&#263; J 2012; 100 (21): 213702
  • Labeling Stem Cells with Ferumoxytol, an FDA-Approved Iron Oxide Nanoparticle JOVE-JOURNAL OF VISUALIZED EXPERIMENTS Castaneda, R. T., Khurana, A., Khan, R., Daldrup-Link, H. E. 2011

    Abstract

    Stem cell based therapies offer significant potential for the field of regenerative medicine. However, much remains to be understood regarding the in vivo kinetics of transplanted cells. A non-invasive method to repetitively monitor transplanted stem cells in vivo would allow investigators to directly monitor stem cell transplants and identify successful or unsuccessful engraftment outcomes. A wide range of stem cells continues to be investigated for countless applications. This protocol focuses on 3 different stem cell populations: human embryonic kidney 293 (HEK293) cells, human mesenchymal stem cells (hMSC) and induced pluripotent stem (iPS) cells. HEK 293 cells are derived from human embryonic kidney cells grown in culture with sheared adenovirus 5 DNA. These cells are widely used in research because they are easily cultured, grow quickly and are easily transfected. hMSCs are found in adult marrow. These cells can be replicated as undifferentiated cells while maintaining multipotency or the potential to differentiate into a limited number of cell fates. hMSCs can differentiate to lineages of mesenchymal tissues, including osteoblasts, adipocytes, chondrocytes, tendon, muscle, and marrow stroma. iPS cells are genetically reprogrammed adult cells that have been modified to express genes and factors similar to defining properties of embryonic stem cells. These cells are pluripotent meaning they have the capacity to differentiate into all cell lineages. Both hMSCs and iPS cells have demonstrated tissue regenerative capacity in-vivo. Magnetic resonance (MR) imaging together with the use of superparamagnetic iron oxide (SPIO) nanoparticle cell labels have proven effective for in vivo tracking of stem cells due to the near microscopic anatomical resolution, a longer blood half-life that permits longitudinal imaging and the high sensitivity for cell detection provided by MR imaging of SPIO nanoparticles. In addition, MR imaging with the use of SPIOs is clinically translatable. SPIOs are composed of an iron oxide core with a dextran, carboxydextran or starch surface coat that serves to contain the bioreactive iron core from plasma components. These agents create local magnetic field inhomogeneities that lead to a decreased signal on T2-weighted MR images. Unfortunately, SPIOs are no longer being manufactured. Second generation, ultrasmall SPIOs (USPIO), however, offer a viable alternative. Ferumoxytol (FerahemeTM) is one USPIO composed of a non-stoichiometric magnetite core surrounded by a polyglucose sorbitol carboxymethylether coat. The colloidal, particle size of ferumoxytol is 17-30 nm as determined by light scattering. The molecular weight is 750 kDa, and the relaxivity constant at 2T MRI field is 58.609 mM(-1) sec(-1) strength. Ferumoxytol was recently FDA-approved as an iron supplement for treatment of iron deficiency in patients with renal failure. Our group has applied this agent in an "off label" use for cell labeling applications. Our technique demonstrates efficient labeling of stem cells with ferumoxytol that leads to significant MR signal effects of labeled cells on MR images. This technique may be applied for non-invasive monitoring of stem cell therapies in pre-clinical and clinical settings.

    View details for DOI 10.3791/3482

    View details for Web of Science ID 000209222200040

  • Acute necrotizing pancreatitis following splenic artery embolization. Tropical gastroenterology : official journal of the Digestive Diseases Foundation Khurana, A., Abdel Khalek, M., Brown, J., Barry, B., Jaffe, B. M., Kandil, E. 2011; 32 (3): 226-229

    View details for PubMedID 22332342

  • MR tracking of macrophage migration into matrix assosciated stem cell transplants via an indirect clinically applicable labeling technique Investigative Radiology Khurana A, Nejadnik H, Castaneda R, Gawande R, Derugin N, Pisani L, Daldrup-Link HE. 2011; 46 (11): 740
  • Labeling stem cells with ferumoxytol, an FDA-approved iron oxide nanoparticle. Journal of visualized experiments : JoVE Castaneda, R. T., Khurana, A., Khan, R., Daldrup-Link, H. E. 2011: e3482-?

    Abstract

    Stem cell based therapies offer significant potential for the field of regenerative medicine. However, much remains to be understood regarding the in vivo kinetics of transplanted cells. A non-invasive method to repetitively monitor transplanted stem cells in vivo would allow investigators to directly monitor stem cell transplants and identify successful or unsuccessful engraftment outcomes. A wide range of stem cells continues to be investigated for countless applications. This protocol focuses on 3 different stem cell populations: human embryonic kidney 293 (HEK293) cells, human mesenchymal stem cells (hMSC) and induced pluripotent stem (iPS) cells. HEK 293 cells are derived from human embryonic kidney cells grown in culture with sheared adenovirus 5 DNA. These cells are widely used in research because they are easily cultured, grow quickly and are easily transfected. hMSCs are found in adult marrow. These cells can be replicated as undifferentiated cells while maintaining multipotency or the potential to differentiate into a limited number of cell fates. hMSCs can differentiate to lineages of mesenchymal tissues, including osteoblasts, adipocytes, chondrocytes, tendon, muscle, and marrow stroma. iPS cells are genetically reprogrammed adult cells that have been modified to express genes and factors similar to defining properties of embryonic stem cells. These cells are pluripotent meaning they have the capacity to differentiate into all cell lineages. Both hMSCs and iPS cells have demonstrated tissue regenerative capacity in-vivo. Magnetic resonance (MR) imaging together with the use of superparamagnetic iron oxide (SPIO) nanoparticle cell labels have proven effective for in vivo tracking of stem cells due to the near microscopic anatomical resolution, a longer blood half-life that permits longitudinal imaging and the high sensitivity for cell detection provided by MR imaging of SPIO nanoparticles. In addition, MR imaging with the use of SPIOs is clinically translatable. SPIOs are composed of an iron oxide core with a dextran, carboxydextran or starch surface coat that serves to contain the bioreactive iron core from plasma components. These agents create local magnetic field inhomogeneities that lead to a decreased signal on T2-weighted MR images. Unfortunately, SPIOs are no longer being manufactured. Second generation, ultrasmall SPIOs (USPIO), however, offer a viable alternative. Ferumoxytol (FerahemeTM) is one USPIO composed of a non-stoichiometric magnetite core surrounded by a polyglucose sorbitol carboxymethylether coat. The colloidal, particle size of ferumoxytol is 17-30 nm as determined by light scattering. The molecular weight is 750 kDa, and the relaxivity constant at 2T MRI field is 58.609 mM(-1) sec(-1) strength. Ferumoxytol was recently FDA-approved as an iron supplement for treatment of iron deficiency in patients with renal failure. Our group has applied this agent in an "off label" use for cell labeling applications. Our technique demonstrates efficient labeling of stem cells with ferumoxytol that leads to significant MR signal effects of labeled cells on MR images. This technique may be applied for non-invasive monitoring of stem cell therapies in pre-clinical and clinical settings.

    View details for DOI 10.3791/3482

    View details for PubMedID 22083287

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