@article{timms2024super,

title = {Super High Contrast USPIO-Enhanced Cerebrovascular Angiography Using Ultrashort Time-to-Echo MRI},

author = {Liam Timms and Tianyi Zhou and Ju Qiao and Codi Gharagouzloo and Vishala Mishra and Rita Maria Lahoud and John W Chen and Mukesh Harisinghani and Srinivas Sridhar},

year  = {2024},

date = {2024-01-01},

journal = {International Journal of Biomedical Imaging},

volume = {2024},

number = {1},

pages = {9763364},

publisher = {Hindawi},

keywords = {MRI},

pubstate = {published},

tppubtype = {article}

}

@article{timms2021ferumoxytol,

title = {Ferumoxytol-enhanced ultrashort TE MRA and quantitative morphometry of the human kidney vasculature},

author = {Liam Timms and Tianyi Zhou and Yue Lyu and Ju Qiao and Vishala Mishra and Rita Maria Lahoud and Gayatri Veeramani Jayaraman and Andrew S Allegretti and David Drew and Ravi T Seethamraju and others},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Abdominal Radiology},

volume = {46},

pages = {3288–3300},

publisher = {Springer US},

keywords = {MRI},

pubstate = {published},

tppubtype = {article}

}

@article{qiao2019data,

title = {Data on MRI brain lesion segmentation using K-means and Gaussian Mixture Model-Expectation Maximization},

author = {Ju Qiao and Xuezhu Cai and Qian Xiao and Zhengxi Chen and Praveen Kulkarni and Craig Ferris and Sagar Kamarthi and Srinivas Sridhar},

year  = {2019},

date = {2019-01-01},

journal = {Data in brief},

volume = {27},

pages = {104628},

publisher = {Elsevier},

abstract = {The data in this article provide details about MRI lesion segmentation using K-means and Gaussian Mixture Model-Expectation Maximization (GMM-EM) algorithms. Both K-means and GMM-EM algorithms can segment lesion area from the rest of brain MRI automatically. The performance metrics (accuracy, sensitivity, specificity, false positive rate, misclassification rate) were estimated for the algorithms and there was no significant difference between K-means and GMM-EM. In addition, lesion size does not affect the accuracy and sensitivity for either method.},

keywords = {MRI},

pubstate = {published},

tppubtype = {article}

}

@article{gharagouzloo2017quantitative,

title = {Quantitative vascular neuroimaging of the rat brain using superparamagnetic nanoparticles: New insights on vascular organization and brain function},

author = {Codi A Gharagouzloo and Liam Timms and Ju Qiao and Zihang Fang and Joseph Nneji and Aniket Pandya and Praveen Kulkarni and Anne L van de Ven and Craig Ferris and Srinivas Sridhar},

year  = {2017},

date = {2017-01-01},

journal = {Neuroimage},

volume = {163},

pages = {24--33},

publisher = {Academic Press},

abstract = {A method called Quantitative Ultra-Short Time-to-Echo Contrast Enhanced (QUTE-CE) Magnetic Resonance Imaging (MRI) which utilizes superparamagnetic iron oxide nanoparticles (SPIONs) as a contrast agent to yield positive contrast angiograms with high clarity and definition is applied to the whole live rat brain. QUTE-CE MRI intensity data are particularly well suited for measuring quantitative cerebral blood volume (qCBV). A global map of qCBV in the awake resting-state with unprecedented detail was created via application of a 3D MRI rat brain atlas with 173 segmented and annotated brain areas. From this map we identified two distributed, integrated neural circuits showing the highest capillary densities in the brain. One is the neural circuitry involved with the primary senses of smell, hearing and vision and the other is the neural circuitry of memory. Under isoflurane anesthesia, these same circuits showed significant decreases in qCBV suggesting a role in consciousness. Neural circuits in the brainstem associated with the reticular activating system and the maintenance of respiration, body temperature and cardiovascular function showed an increase in qCBV with anesthesia. During awake CO2 challenge, 84 regions showed significant increases relative to an awake baseline state. This CO2 response provides a measure of cerebral vascular reactivity and regional perfusion reserve with the highest response measured in the somatosensory cortex. These results demonstrate the utility of QUTE-CE MRI for qCBV analysis and offer a new perspective on brain function and vascular organization.},

keywords = {MRI},

pubstate = {published},

tppubtype = {article}

}

@article{wang2015integrity,

title = {Integrity of 111In-radiolabeled superparamagnetic iron oxide nanoparticles in the mouse},

author = {Haotian Wang and Rajiv Kumar and Dattatri Nagesha and Richard I Duclos Jr and Srinivas Sridhar and Samuel J Gatley},

year  = {2015},

date = {2015-01-01},

journal = {Nuclear medicine and biology},

volume = {42},

number = {1},

pages = {65--70},

publisher = {Elsevier},

abstract = {Introduction

Iron-oxide nanoparticles can act as contrast agents in magnetic resonance imaging (MRI), while radiolabeling the same platform with nuclear medicine isotopes allows imaging with positron emission tomography (PET) or single-photon emission computed tomography (SPECT), modalities that offer better quantification. For successful translation of these multifunctional imaging platforms to clinical use, it is imperative to evaluate the degree to which the association between radioactive label and iron oxide core remains intact in vivo.



Methods

We prepared iron oxide nanoparticles stabilized by oleic acid and phospholipids which were further radiolabeled with 59Fe, 14C-oleic acid, and 111In.



Results

Mouse biodistributions showed 111In preferentially localized in reticuloendothelial organs, liver, spleen and bone. However, there were greater levels of 59Fe than 111In in liver and spleen, but lower levels of 14C.



Conclusions

While there is some degree of dissociation between the 111In labeled component of the nanoparticle and the iron oxide core, there is extensive dissociation of the oleic acid component.},

keywords = {MRI, Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{gharagouzloo2015quantitative,

title = {Quantitative contrast-enhanced MRI with superparamagnetic nanoparticles using ultrashort time-to-echo pulse sequences},

author = {Codi Amir Gharagouzloo and Patrick N McMahon and Srinivas Sridhar},

year  = {2015},

date = {2015-01-01},

journal = {Magnetic resonance in medicine},

volume = {74},

number = {2},

pages = {431--441},

keywords = {MRI, Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{sridhar2014wavelet,

title = {Wavelet Transform Techniques for Image Compression-An Evaluation},

author = {S Sridhar and Rajesh P Kumar and KV Ramanaiah},

year  = {2014},

date = {2014-01-01},

journal = {International journal of image, graphics and signal processing},

volume = {6},

number = {2},

pages = {54},

publisher = {Modern Education and Computer Science Press},

abstract = {A vital problem in evaluating the picture quality of an image compression system is the difficulty in describing the amount of degradation in reconstructed image, Wavelet transforms are set of mathematical functions that have established their viability in image compression applications owing to the computational simplicity that comes in the form of filter bank implementation. The choice of wavelet family depends on the application and the content of image. Proposed work is carried out by the application of different hand designed wavelet families like Haar, Daubechies, Biorthogonal, Coiflets and Symlets etc on a variety of bench mark images. Selected benchmark images of choice are decomposed twice using appropriate family of wavelets to produce the approximation and detail coefficients. The highly accurate approximation coefficients so produced are further quantized and later Huffman encoded to eliminate the psychovisual and coding redundancies. However the less accurate detailed coefficients are neglected. In this paper the relative merits of different Wavelet transform techniques are evaluated using objective fidelity measures- PSNR and MSE, results obtained provide a basis for application developers to choose the right family of wavelet for image compression matching their application.},

keywords = {MRI},

pubstate = {published},

tppubtype = {article}

}

@article{sawantpolymeric,

title = {Polymeric Magnetomicelles As a Probe for MRI Imaging: Characterization and Mri Properties},

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

abstract = {Superparamagnetic iron oxide nanoparticles (SPIONs) coated with silane were prepared and entrapped in polymeric micelles made from PEG-PE using hepes-buffered saline pH 7.4. The SPIONs entrapped in these micelles had excellent stability and did tend to aggregate at the conditions store. In contrast “plain” SPIONs collapsed from solution and did not show any ability to remain dispersed. SPION-micelles thus prepared have shown an improved relaxivity at low concentration of entrapped SPIONs, which makes them to be promising contrast agents for T2 MRI imaging.},

keywords = {MRI},

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{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}

}