Publications

@article{barlowmicroencapsulation,

title = {Microencapsulation of Bacteria for Controlled Release of Bioactives},

author = {Jacob Barlow and Kevin Gozzi and Chase Kelley and Anne Van De Ven-Moloney and Yunrong Chai and Srinivas Sridhar},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{baldwinparp,

title = {PARP Inhibitor Nanotherapy for Cancer Treatment},

author = {Paige Baldwin and Anders Ohman and Anne van de Ven and Daniela Dinulescu and Srinivas Sridhar},

abstract = {Poly (ADP-ribose) Polymerase (PARP) plays an important role in a number of DNA repair pathways. PARP inhibitors, such as Olaparib exploit the concept of synthetic lethality by selectively targeting cancer cells with defective DNA repair pathways, while leaving healthy cells with multiple repair pathways unharmed. These drugs are currently only available in oral form which results in limited bioavailability, poor tumor accumulation, and systemic toxicity. Nanoparticle formulations of Olaparib were developed to allow intravenous (IV) or intraperitoneal (IP) delivery, providing greater bioavailability and tumor accumulation, while limiting systemic toxicities. NanoOlaparib was synthesized and characterized before further testing in vitro and in vivo. In vitro it has been tested in a panel of ovarian cancer cell lines to elucidate sensitivity profiles. NanoOlaparib was also tested in an ovarian cancer IP spread model. Animals were treated IP with NanoOlaparib alone, and in combination with cisplatin. Bioluminescence imaging illustrated that NanoOlaparib administered IP daily resulted in a greater inhibition of tumor growth than those treated with oral Olaparib daily. Radiosensitization with NanoOlaparib was tested in a radiation resistant prostate cancer cell line, FK01 and a xenograft model with the same cells to mimic castration resistant prostate cancer. The FK01 xenografts are highly radioresistant with little difference between untreated and radiation only animals. NanoOlaparib delays tumor growth, while the combination of radiation and NanoOlaparib shrinks tumors. These results show that NanoOlaparib amplifies the therapeutic efficacy of PARP …},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{weiproperties,

title = {PROPERTIES OF SUPERCOOLED LiCl RH O SOLUTIONS},

author = {YAN-ZHEN WEI and S SRIDHAR},

abstract = {The relation between the dynamics of dielectric relaxation, the glass-forming ability and properties in the supercooled state of LiCl: RH, O solutions are investigated, via measurements of the dielectric spectra between 45 MHz and 20 GHz and temperatures between 210 K and 300 K and concentrations R< 20. For high concentration glass-forming solutions, a close correspondence between the temperature dependencies of the Cole-Cole relaxation time t, the conductivity, and the viscosity, is observed.,(T) is well-described by a power law form (TT,)', with T.,-205 K and y-2, a form motivated by mode-coupling theory. The data suggest that non-Debye response at room temperature is associated with the ability to vitrify at low temperatures. A microscopic basis for the avoidance of crystallization is provided by obtaining from the dielectric data the mean radius available to a water molecule, which is shown to approach 19 …},

keywords = {Chemical & Biological Physics},

pubstate = {published},

tppubtype = {article}

}

@article{kumarsupporting,

title = {Supporting information Nanoparticles based brachytherapy spacers for delivery of localized combined chemo-radiation therapy},

author = {Rajiv Kumar and Jodi Belz and Stacey Markovic and Tej Jhadav and William Fowle and Mark Niedre and Robert Cormack and Mike G Makrigiorgos and Srinivas Sridhar},

abstract = {Synthesis of NIR fluorescent Silica nanoparticles: The synthesis of conCy7. 5-SNPs was carried out using oil-inwater microemulsion method, following a previously reported protocol with several modifications.(1-2) For conjugating the Cy7. 5 fluorophore in the SNPs, Cy7. 5-NHS ester was first conjugated to a silane precursor using aminopropyltriethoxy silane. 5 mg Cy 7.5 NHS ester (6.4 μmol), 1.77 mg APTES (8 μmol) and 10 μl neat triethylamine were added to 1 ml of anhydrous DMSO and stirred over night at room temperature under Ar atmosphere. The crude mixture was purified using EtOAc-hexane mixture, dried and resuspended in 1ml of DMSO. For synthesizing the Cy7. 5 conjugated ORMOSIL nanoparticles, 10ml of 2.2%(w/v) surfactant AOT solution was prepared in HPLC grade water followed by addition of 600 μl of n-butanol and 50 μl of Cy7. 5-silane under vigorous stirring at rt After 15 min of stirring 100ul of neat VTES was added and resultant reaction mixture was stirred for another 45 minutes. Finally 10ul of NH4OH was added and reaction was allowed to stir overnight. The nanoparticles suspension was then dialyzed against distilled water for 48h at room temperature, using a cellulose membrane with a cut-off size of 12-14 kDa. Following dialysis, the nanoparticles were sterile filtered and stored at 4 C for future use.

Fabrication of INCeRT spacers: For fabricating the spacers, the extracted SNPs from the aqueous mother liquor required a careful assessment, in terms of solvent compatibility with the PLGA polymer, so that both can be dispersed in a single phase without disturbing the integrity of the nanoparticles and the …},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{srikanthevidence,

title = {Evidence for Short-range Magnetic Order and Spin-gap? The broad peaks between 400 cm},

author = {H Srikanth and B Revcolevschi and S Sridhar and L Pinsard and A Revcolevschi},

keywords = {Magnetism},

pubstate = {published},

tppubtype = {article}

}

@article{harika4analysis,

title = {Analysis of Different Multiplication Algorithms & FPGA Implementation},

author = {K Harika and BV Swetha and B Renuka and Lakshman D Rao and S Sridhar},

journal = {IOSR Journal of VLSI and Signal Processing (IOSR-JVSP)},

volume = {4},

number = {2},

pages = {29--35},

keywords = {Quantum Chaos},

pubstate = {published},

tppubtype = {article}

}

@article{kennedyli,

title = {li. EQUENCY-UEPENDENCE OF THE MICROWAVE SURFACE RESISTANCE OF CERAMIC У, Вп2Си30 „},

author = {WL Kennedy and C Zahopoulos and S Sridhar},

abstract = {The frequency dependence оГ the surface resistance Rj of ceramic Y^ BaaGujÓgv; ik measured between 5 GHz and 20 GJlz in both the normal a. nd superconducting states. Tlie measurements were carried out using a, fully superconducting resonant cavity T made of the oxide superconductor. The surface resistance was found to vary as R, к f, with 7= 0.0±0.2 at 118 1С in the normal state, and у= 2.0±0.3 in the superconducting state. The normal stale results are consistent in magnitude and frequency dependence with the classical skin effect, and the quadratic dependence in the superconducting state clearly indicates a local electrodynamics оГ a Josephson-coupled network.

The microwave response of the recently discovered oxide superconductors is of considerable interest, both from a fundamental scientific and technological viewpoint. Several measurements of the temperature dependence of the surface …},

keywords = {Superconductivity},

pubstate = {published},

tppubtype = {article}

}

@article{balincreased,

title = {Increased Nanoparticle Uptake Under Disturbed Flow-Induced Degraded Glycocalyx Conditions},

author = {Nandita Bal and Ming Cheng and Rajiv Kumar and Srinivas Sridhar and Eno Ebong},

abstract = {Results: The partial LCA ligation model achieved the goal of creating a vessel with disturbed flow and provided a convenient comparison with a healthy RCA experiencing streamlined flow. The vessel walls of the LCA also exhibited a more discontinuous GCX layer on the intima as compared to the RCA, decreasing from 76.3±10.2% in the RCA to 21.2±5.9% in the LCA. This observable dysfunction correlated to increased nanoparticle uptake, as the LCA took in approximately 2.5-fold more GNS than the RCA did, based on the fluorescence signal detected in the histology images. This was imaged at 10 times magnification (Fig 1) and 63 times magnification (Fig 2).

Conclusions: A partial LCA ligation was performed to acutely disturb blood flow in a mouse vessel and observe resultant endothelial GCX dysfunction as well as passive targeting of GNS to affected areas. The affected LCA exhibited lack of continuous GCX layer, as well as increased localization of PEG coated GNS that are designed to deliver drug therapies. These results indicate that vessel and GCX dysfunction, both precursors of atherosclerosis and cardiovascular disease, can be induced in a mouse model to study targeted drug delivery. Passive nanoparticle uptake differences between the healthy RCA and disturbed LCA indicate a role of GCX infiltration of nanoparticles to the endothelial cells. Targeting dysfunctional vessels based on the GCX offers a new approach in cardiovascular disease therapy and prevention.},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{gharagouzloofunctional,

title = {Functional neuroimaging using dynamic radial 3D UTE pulse sequences},

author = {Codi Amir Gharagouzloo and Chao Ma and Eline E Verwer and Joseph B Mandeville and Chuan Huang and Srinivas Sridhar and Georges El Fakhri and Dustin W Wooten and Marc D Normandin},

abstract = {Functional MR neuroimaging is an essential tool for studying brain activity. Cerebral blood volume (CBV) is an important indicator of brain function, but measurements are typically qualitative or relative. Furthermore, warping and signal drift necessitate significant image pre-processing with standard EPI acquisition. In this work, we utilize a radial 3D UTE pulse sequence with optimized acquisition parameters determined from phantoms and modeling. Feasibility of dynamic UTE as a functional neuroimaging method is demonstrated in non-human primates receiving NBOH-2C-CN, a 5-HT2A receptor agonist. CBV is measured dynamically throughout the whole brain and shown to agree well with an analogous EPI experiment.



PURPOSE

The three primary physiological indicators of neural activity in fMRI are changes in cerebral blood volume (CBV), blood flow and oxygenated state of hemoglobin.To isolate the CBV-induced signal change, T2*-weighted echo-planar imaging (EPI) sequences are commonly utilized with intravascular contrast agent to overshadow contrast from changes in blood oxygenation and enhance signal from CBV changes. While EPI sequences are fast, they are prone to significant distortion artifact. Additionally, macroscopic susceptibility artifacts confound the MR signal and are difficult to separate from baseline blood oxygenation level dependent (BOLD) effects; thus results are qualitative. Ultra-short time-to-echo (UTE) sequences are insensitive to susceptibility changes and extravoxular signal dephasing. Thus, we propose to use quantitative UTE contrast-enhanced (QUTE-CE) MRI to measure CBV changes dynamically.



METHODS

QUTE-CE MRI is the combination of acquisition with an optimized 3D UTE pulse sequence and an intra-vascular contrast agent1 to render a highly quantitative signal. Ferumoxytol (Feraheme, AMAG Pharmaceuticals, Waltham, Massachusetts, USA) was used for contrast.



Relaxation rates were measured in 1% heparinized whole-calf-blood (Fig. 1a,-c) and modeling with the spoiled gradient echo (SPGR) equation was used to determine optimized parameters for efficient dynamic scans (Fig. 1d). CBV is calculated by simple partial volume calculations. The effect of signal modification by vascular water molecule exchange is suppressed with low TR and high FA2. Modeling signal intensity with two compartments:



IM=fBIb+(1−fB)IT



where, IT is the brain tissue intensity, IB is the blood intensity and fB is the fraction of the voxel occupied by blood. For each image volume, CBV is calculated voxel-by-voxel by subtracting a pre-contrast image then scaling the results by the blood intensity as determined in a large vessel:



fB=CBV=I,M−IMI,B−IB



Animal experiments were conducted under an approved IACUC protocol. A dynamic QUTE-CE study was performed with ferumoxytol on a non-human primate (NHP) with NBOH-2C-CN, a potent and selective 5-HT2A receptor agonist, and results were compared to the current gold standard EPI + ferumoxytol imaging. All imaging was performed on a Siemens 3T Tim Trio magnet. NHPs were anesthetized throughout the scan with isoflurane (1-3%). EPI and UTE scans consisted of three imaging phases: pre-contrast followed by a bolus of 10mg/kg ferumoxytol post-contrast and then administration of 50 mcg/kg of NBOH-2C-CN. Single-shot EPI was accelerated in the phase-encode direction by a factor of two providing an isotropic spatial resolution of 1.3mm and TE=23ms.



RESULTS

QUTE-CE pre-contrast images rendered dark blood with a small amount of tissue contrast in NHPs (Fig. 2a). Bright positive contrast of the blood was achieved after injection of ferumoxytol (Fig. 2b-d). Vasculature was clearly visible and all parts of the anatomy were free of image warping (Fig 2a-c). In contrast, time-averaged EPI data equal to the duration of the dynamic UTE scan exhibited significant signal dropout in the anterior and posterior brain, with obvious image warping (Fig 2f). The same custom-built 8-channel receive coil was used in both acquisitions. Maps of absolute CBV obtained from pre- and post-contrast UTE images are of high quality and have quantitative values consistent with expectation (Fig. 2e).



A dynamic QUTE-CE scan was performed with 1m57s time-resolution. Total scan duration was ~1.5 hours, including 48min prior to NBOH-2C-CN challenge and ~52min of data featuring drug-induced CBV changes. NBOH-2C-CN primarily affect the cortex where 5-HT2A receptors exist in high density. CBV measurements from the full cortex were compared to a separate identical experiment with EPI acquisition. Absolute CBV was measured in the cortex using the dynamic UTE method (Fig. 3b). Relative CBV changes measured by EPI and UTE exhibit strong correlation of temporal features of the response and reasonable agreement in magnitude (Fig 3c).



DISCUSSION

Sparse radial sampling is being investigated to accelerate acquisition time for each UTE volume, thereby improving the dynamic frame rate. The apparent disadvantage of a T1-based method given the high r2/r1 ratio of ferumoxytol might well be mitigated in the context of slow frequency changes, such as when study pharmacological responses3. Similar effects are presumed to occur for ASL in relation to BOLD signal4. In analogy to ASL, which has smaller signal changes than BOLD, smaller absolute signal changes in T1-based methods might find application at low frequencies due to the absolute normalization, which could remove much of the drift.

CONCLUSION

To conclude, we achieved time-resolved functional imaging of brain vasculature in NHPs with a radial 3D UTE pulse sequence. Images do not exhibit spatial warping seen in EPI data and yields quantitative CBV measurements devoid of time-varying signal drift. Without baseline correction, the technique produces relative results that agree well with those obtained in a separate EPI experiment.

Acknowledgements

This work was supported in part by funding from NIH R01MH100350 (MDN) and by NIH T32EB013180 (GEF).

References

1. Gharagouzloo, C. A., Mcmahon, P. N. & Sridhar, S. Quantitative contrast-enhanced MRI with superparamagnetic nanoparticles using ultrashort time-to-echo pulse sequences. Magnetic Resonance in Medicine (2014). doi:10.1002/mrm.25426.



2. Kim, Y. R., Rebro, K. J. & Schmainda, K. M. Water exchange and inflow affect the accuracy of T1-GRE blood volume measurements: Implications for the evaluation of tumor angiogenesis. Magn. Reson. Med. 47, 1110–1120 (2002).



3. Jenkins, B. G. Pharmacologic magnetic resonance imaging (phMRI): Imaging drug action in the brain. NeuroImage 62, 1072–1085 (2012).



4. Wang, J. et al. Arterial spin labeling perfusion fMRI with very low task frequency. Magn. Reson. Med. 49, 796–802 (2003).},

keywords = {MRI},

pubstate = {published},

tppubtype = {article}

}

@article{srikanthhigh,

title = {HIGH FREQUENCY MAGNETO-ELECTRODYNAMICS OF Lal. xSrxMnO 3 SINGLE},

author = {H Srikanth and B Revcolevschi and S Sridhar and L Pinsard and A Revcolevschi},

abstract = {The radio frequency (RF) response of La1-xSrxMnO3 single crystals reveal a variety of features associated with the structural, electronic and magnetic properties of the system. The resonance technique operating at ∼ 4 MHz employed in this study is sensitive to small changes in both the magnetic susceptibility and resistivity of the samples. Very sharp changes in frequency are observed at the ferromagnetic (FM) and structural phase transitions in both the metallic (x = 0.175) and insulating (0.125) crystals studied.



In addition to the known transitions identified as FM and orthorhombic distortions, our experiments show rich structures which are not observed in conventional DC magnetization and transport experiments. Our results demonstrate that RF experiments are ideally suited to investigate the complex phase diagram in the manganites.



The colossal frequency change that we observe at the FM transition in the La1-xSrxMnO3 crystals is indicative of the enormous potential for using these materials in high frequency switching applications.},

keywords = {Magnetism},

pubstate = {published},

tppubtype = {article}

}

@article{kuskopublication,

title = {Publication: Journal of Superconductivity Pub Date: 2001},

author = {C Kusko and Z Zhai and RS Markiewicz and S Sridhar},

keywords = {Superconductivity},

pubstate = {published},

tppubtype = {article}

}

@article{sawantdeveloping,

title = {Developing superparamagnetic iron oxide nanoparticles as tumor-specific magnetic resonance imaging (MRI) contrast agents},

author = {RM Sawant and E Gultepe and D Nagesha and S Sridhar and VP Torchilin},

abstract = {Superparamagnetic iron oxide nanoparticles (SPION) have received increased interest due to their characteristic small size ca 4-10 nm and excellent T2-type MRI contrast properties. However, uncoated-“plain” SPION have a tendency to aggregate and thus are not stable at normal physiological conditions. In this work we load the SPION in polymeric polyethylene glycol phosphatidyl ethanolamine (PEG-PE) micelles and additionally surface-modify with anticancer anti-nucleosome antibody 2C5.(mAb 2C5). SPION-loaded PEG-PE micelles were stable with the size ranging from 20 to 40 nm. The conjugation of mAb 2C5 was gentle and there was almost no loss in activity of the antibody after conjugation. SPION-loaded mAb 2C5 immunomicelles were able to recognize and bind with human breast cancer MCF-7 cells in vitro significantly higher when compared to SPION-loaded “plain” micelles or SPION-loaded “non …},

keywords = {MRI},

pubstate = {published},

tppubtype = {article}

}