However, the long acquisition time in MRSI is a deterrent to its inclusion in clinical protocols due to associated costs, patient discomfort (especially in pediatric patients under anesthesia), and higher susceptibility to motion artifacts. Acceleration strategies like compressed sensing (CS) permit faithful reconstructions even when the k-space is undersampled well below the Nyquist limit. CS is apt for MRSI as spectroscopic data are inherently sparse in multiple dimensions of space and frequency in an appropriate transform domain, for e.g. the wavelet domain. The objective of this research was three-fold: firstly on the preclinical front, to prospectively speed-up spectrally-edited MRSI using CS for rapid mapping of lactate and capture associated changes in response to therapy. Secondly, to retrospectively evaluate CS-MRSI in pediatric patients scanned for various brain-related concerns. Thirdly, to implement prospective CS-MRSI acquisitions on a clinical magnetic resonance imaging (MRI) scanner for fast spectroscopic imaging studies. Both phantom and in vivo results demonstrated a reduction in the scan time by up to 80%, with the accelerated CS-MRSI reconstructions maintaining high spectral fidelity and statistically insignificant errors as compared to the fully sampled reference dataset. Optimization of CS parameters involved identifying an optimal sampling mask for CS-MRSI at each acceleration factor. It is envisioned that time-efficient MRSI realized with optimized CS acceleration would facilitate the clinical acceptance of routine MRSI exams for a quantitative mapping of important biomarkers.
Amikagel’s properties were chemo-mechanically tunable and directly impacted the outcome of tumor dormancy or relapse. Exposure of dormant spheroids to weakly stiff and adhesive formulation of Amikagel resulted in significant relapse, mimicking the response to changes in extracellular matrix around dormant tumors. Relapsed cells showed significant differences in their metastatic potential compared to the cells that remained dormant after the induction of relapse. Further, the dissertation discusses the use of Amikagels as novel pDNA binding resins in microbead and monolithic formats for potential use in chromatographic purifications. High abundance of amino groups allowed their utilization as novel anion-exchange pDNA binding resins. This dissertation discusses Amikagel formulations for pDNA binding, metastatic cancer cell separation and novel drug discovery against tumor dormancy and relapse.
The glucose metabolism level reflects cell proliferative status. A polymeric glucose ratiometric sensor comprising poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) and poly[2-(methacryloyloxy)ethyl]trimethylammonium chloride (PMAETMA) was synthesized. Cellular internalization and glucose response of the polymer within HeLa cells were investigated.
Functional and molecular cell-to-cell variability is pivotal at the cellular, tissue and whole-organism levels. Yet, the ultimate goal of directly correlating the function of the individual cell with its biomolecular profile remains elusive. We present a platform for integrated analysis of functional and transcriptional phenotypes in the same single cells. We investigated changes in the cellular respiration and gene expression diversity resulting from adaptation to repeated episodes of acute hypoxia in a premalignant progression model. We find differential, progression stage-specific alterations in phenotypic heterogeneity and identify cells with aberrant phenotypes. To our knowledge, this study is the first demonstration of an integrated approach to elucidate how heterogeneity at the transcriptional level manifests in the physiologic profile of individual cells in the context of disease progression.